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26 episodes with synaptic plasticity
2 episodes with synaptic plasticity
2 episodes with synaptic plasticity
2 episodes with synaptic plasticity
3 episodes with synaptic plasticity
2 episodes with synaptic plasticity
5 episodes with synaptic plasticity
In this episode, we're diving deep into GLP-1 agonists, a topic that has sparked considerable debate within the fitness and health communities. Our special guest, Anthony Castor, brings a wealth of knowledge as the first non-physician to earn a fellowship with the Seed Scientific Research and Performance Institute. Together, we'll address controversies, debunk myths, and uncover the multi-faceted benefits of GLP-1 agonists far beyond their well-known role in weight loss and diabetes management. We'll explore their neuroprotective effects, benefits in managing neurodegenerative diseases like Alzheimer's and Parkinson's, and their surprising impact on cognitive decline, addiction, and ADHD. Moreover, we'll break down complex mechanisms, historical context, and real-world applications in an easily digestible format. Stay tuned as we demystify GLP-1 agonists and reveal how they can enhance not only physical but also mental resilience. Anthony Castor, a health advocate and educator, delves into the intricate world of peptides and their multifaceted benefits. With a passion for making complex biochemical processes understandable, Anthony focuses on the potent impacts of GLP-1 (glucagon-like peptide-1), GIP (gastric inhibitory polypeptide), and myelin, among others. By demystifying how these peptides interact and function together, Anthony aims to shift public perception and drive forward significant improvements in health. Known for his use of analogies to clarify scientific concepts, Anthony is committed to educating people on the transformative potential of these sophisticated biochemical tools. Anthony's Website: https://www.castoremethod.com Instagram: https://www.instagram.com/anthonycastore/ Join Duffin Community & Education: https://www.skool.com/endless-evolution-8560/about www.chrisduffin.com
Emilia Lefevre discusses her paper, “Differential Patterns of Synaptic Plasticity in the Nucleus Accumbens Caused by Continuous and Interrupted Morphine Exposure,” published in Vol. 43, Issue 2 of JNeurosci in 2023, with Megan Sansevere from SfN's Journals' staff. Find the rest of the Spotlight collection here. With special guest: Emilia Lefevre Hosted by: Megan Sansevere On Neuro Current, we delve into the stories and conversations surrounding research published in the journals of the Society for Neuroscience. Through its publications, JNeurosci, eNeuro, and the History of Neuroscience in Autobiography, SfN promotes discussion, debate, and reflection on the nature of scientific discovery, to advance the understanding of the brain and the nervous system. Find out more about SfN and connect with us on X, Instagram, and LinkedIn.
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
Explore cutting-edge research at the intersection of neuroscience, space exploration, and medical innovation. Researchers discuss revolutionary experiments with brain organoids cultivated from stem cells, conducted both in terrestrial labs and aboard the International Space Station. They investigate accelerated aging, neuroprotective agents, and potential treatments for conditions like Alzheimer's and ALS. The dialogue also delves into the transformative impact of space environments on scientific discoveries, from understanding bacterial growth to developing novel therapies. Through collaborative efforts, they strive to revolutionize healthcare, offering hope for patients and pushing the boundaries of human knowledge. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39632]
TWiN explains research showing that interaction between glioma cells and neurons in the brain shares mechanistic features with synaptic plasticity that contributes to memory and learning in the healthy brain. Hosts: Vincent Racaniello, Jason Shepherd, and Timothy Cheung Subscribe (free): Apple Podcasts, Google Podcasts, RSS Links for this episode MicrobeTV Discord Server Glioma synapses recruit mechanisms of adaptive plasticity (Nature) Timestamps by Jolene. Thanks! Music is by Ronald Jenkees Send your neuroscience questions and comments to twin@microbe.tv
Dr. Nicole Calakos is the Lincoln Financial Group Distinguished Professor of Neurobiology and Chief of the Movement Disorders section in Neurology at Duke University Medical Center. Research in Nicole's lab examines how the brain learns and adapts to experiences. She studies synaptic plasticity, from the levels of molecules, cells, cell circuits, and behaviors, to understand what goes wrong in disease and how we can harness brain processes to address disease. When she's not working, Nicole enjoys being outdoors, playing sports, running, going mountain biking, and participating in mountain bike races. Her favorite indoor activities include creative cooking and spending time with family and friends. Nicole was awarded her MD and PhD degrees from Stanford University. Afterwards, she completed an internship in Medicine and Residency in Neurology at the University of California, San Francisco School of Medicine. She conducted postdoctoral research at Stanford University before joining the faculty at Duke University in 2005. Nicole has received numerous awards and honors in her career, including the 2023 Korsmeyer award from the American Society of Clinical Investigation and being named an elected Member of the U.S. National Academy of Medicine, a Fellow of the American Association for the Advancement of Science, and a Fellow of the American Society of Clinical Investigators. In our interview, Nicole shares more about her life and science.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.03.551808v1?rss=1 Authors: Ribeiro, F. C., Cozachenco, D., Argyrousi, E. K., Staniszewski, A., Wiebe, S., Calixtro, J. D., Soares-Neto, R., Al-Chami, A., El Sayegh, F., Bermudez, S., Arsenault, E., Cossenza, M., Lacaille, J.-C., Nader, K., Sun, H., De Felice, F. G., Lourenco, M. V., Arancio, O., Aguilar-Valles, A., Sonenberg, N., Ferreira, S. T. Abstract: Impaired synaptic plasticity and progressive memory deficits are major hallmarks of Alzheimer's disease (AD). Hippocampal mRNA translation, required for memory consolidation, is defective in AD. Here, we show that genetic reduction of the translational repressors, Fragile X messenger ribonucleoprotein (FMRP) or eukaryotic initiation factor 4E (eIF4E)-binding protein 2 (4E-BP2), ameliorated the inhibition of hippocampal protein synthesis and memory impairment induced by AD-linked amyloid-b; oligomers (AbOs) in mice. Furthermore, systemic treatment with (2R,6R)-hydroxynorketamine (HNK), an active metabolite of the antidepressant ketamine, prevented deficits in hippocampal mRNA translation, long-term potentiation (LTP) and memory induced by AbOs in mice. HNK activated hippocampal signaling by extracellular signal-regulated kinase 1/2 (ERK1/2), mechanistic target of rapamycin (mTOR), and p70S6 kinase 1 (S6K1)/ribosomal protein S6 (S6), which promote protein synthesis and synaptic plasticity. S6 phosphorylation instigated by HNK was mediated by mTOR in hippocampal slices, while rescue of hippocampal LTP and memory in HNK-treated AbO-infused mice depended on ERK1/2 and, partially, on mTORC1. Remarkably, treatment with HNK corrected LTP and memory deficits in aged APP/PS1 mice. RNAseq analysis showed that HNK reversed aberrant signaling pathways that are upregulated in APP/PS1 mice, including inflammatory and hormonal responses and programmed cell death. Taken together, our findings demonstrate that upregulation of mRNA translation corrects deficits in hippocampal synaptic plasticity and memory in AD models. The results raise the prospect that HNK could serve as a therapeutic to reverse memory decline in AD. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.08.01.551248v1?rss=1 Authors: Baraibar, A. M., Colomer, T., Moreno-Garcia, A., Bernal-Chico, A., Sanchez, E., Utrilla, C., Serrat, R., Soria-Gomez, E., Rodriguez-Antiguedad, A., Araque, A., Matute, C., Marsicano, G., Mato, S. Abstract: Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis (MS) and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in MS initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we measured astrocytic calcium in the experimental autoimmune encephalomyelitis (EAE) model of MS using fiber photometry in freely behaving mice and two-photon imaging ex vivo. We identified the emergence of spontaneously hyperactive cortical astrocytes displaying calcium transients of increased duration as well as dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists during acute EAE disease. Deficits in astrocyte calcium responses are associated to abnormal signaling by Gi and Gq protein coupled receptors in the inflamed cortex and are partially mirrored in cells activated with pro-inflammatory factors both in vitro and ex vivo thus suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, we show that deregulated astrocyte calcium activity is associated to an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall our data identities astrocyte-neuronal network dysfunction as key pathological feature of the inflammatory gray matter that may contribute to MS symptomatology and clinical progression. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539450v1?rss=1 Authors: Niraula, S., Yan, S. S., Subramanian, J. Abstract: Alzheimer's disease is associated with altered neuronal activity, presumably due to impairments in homeostatic synaptic plasticity. Neuronal hyper and hypoactivity are also observed in mouse models of amyloid pathology. Using multicolor two-photon microscopy, we test how amyloid pathology alters the structural dynamics of excitatory and inhibitory synapses and their homeostatic adaptation to altered experience-evoked activity in vivo in a mouse model. The baseline dynamics of mature excitatory synapses and their adaptation to visual deprivation are not altered in amyloidosis. Likewise, the baseline dynamics of inhibitory synapses are not affected. In contrast, despite unaltered neuronal activity patterns, amyloid pathology leads to a selective disruption of homeostatic structural disinhibition on the dendritic shaft. We show that excitatory and inhibitory synapse loss is locally clustered under the nonpathological state, but amyloid pathology disrupts it, indicating impaired communication of changes in excitability to inhibitory synapses. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.02.539020v1?rss=1 Authors: Li, P. Y., Roxin, A. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.01.538923v1?rss=1 Authors: Viana, J. F., Guerra-Gomes, S., Abreu, D. S., Machado, J. L., Barsanti, S., Goncalves, M., Martin-Monteagudo, C., Sardinha, V., Nascimento, D., Tavares, G., Irmler, M., Beckers, J., Korostynski, M., Sousa, N., Navarrete, M., Teixeira-Castro, A., Pinto, L., Oliveira, J. F. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.18.537377v1?rss=1 Authors: Xiao, K., Li, Y., Chitwood, R. A., Magee, J. C. Abstract: Behavioral timescale synaptic plasticity (BTSP) is a type of non-Hebbian synaptic plasticity reported to underlie place field formation in the hippocampal CA1 neurons. Despite this important function, the molecular mechanisms underlying BTSP are poorly understood. The Calcium-calmodulin-dependent protein kinase II (CaMKII) is activated by synaptic transmission-mediated calcium influx and its subsequent phosphorylation is central to synaptic plasticity. Because the activity of CaMKII is known to outlast the event triggering phosphorylation, we hypothesized it could be involved in the extended timescale of the BTSP process. To examine the role of CaMKII in BTSP, we performed whole-cell in-vivo and in-vitro recordings in CA1 pyramidal neurons from mice engineered to have a point mutation at the autophosphorylation site (T286A) causing accelerated signaling kinetics. Here we demonstrate a profound deficit in synaptic plasticity, strongly suggesting that CaMKII signaling is required for BTSP. This study elucidates part of the molecular mechanism of BTSP and provides insight into the function of CaMKII in place cell formation and ultimately learning and memory. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.04.535572v1?rss=1 Authors: Wu, Y., Maass, W. Abstract: Recent experimental studies in the awake brain have identified a new rule for synaptic plasticity that appears to be instrumental for the induction of episodic and conjunctive memories in the mammalian brain: behavioral time scale synaptic plasticity (BTSP)(Bittner et al. (2015, 2017); Grienberger and Magee (2022)). BTSP differs in essential aspects from previously studied rules for synaptic plasticity. But there is so far no theory that enables a principled understanding of the impact of BTSP on the structure of the associative memory that it induces. We extract fundamental mathematical principles from experimental data on BTSP that elucidate the capacity and associative recall capabilities of memory structures that it creates. Predictions of the resulting theory are corroborated by large-scale numerical experiments. In particular, we show that BTSP can create well-separated memory traces for a very large number of memory items, even if these are not orthogonal. Furthermore, BTSP induces the repulsion effect, a well-known fingerprint of memory organization in the human brain, that could not be explained by preceding types of synaptic plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534509v1?rss=1 Authors: El-Oussini, H., Zhang, C.-L., Francois, U., Castelli, C., Lampin Saint-Amaux, A., Lepleux, M., Molle, P., Velez, L., Dejean, C., Lanore, F., Herry, C., Choquet, D., Humeau, Y. Abstract: Consolidation of recent memory depends on hippocampal activities during resting periods that immediately follows the memory encoding. There, Slow Save Sleep phases appear as privileged periods for memory consolidation as hosting the ripple activities, which are fast oscillations generated within the hippocampus whose inactivation leads to memory impairment. If a strong correlation exists between these replays of recent experience and the persistence of behavioural adaptations, the mobilisation, the localization and the importance of synaptic plasticity events in this process is largely unknown. To question this issue, we used cell-surface AMPAR immobilisation to block post-synaptic LTP within the hippocampal region at various steps of the memory process. 1- Our results show that hippocampal synaptic plasticity is engaged during the consolidation but is dispensable during the encoding or recall of a working memory based spatial memory task. 2- Blockade of plasticity during sleep leads to apparent forgetting of the encoded rule. 3- In vivo recordings of ripple activities during resting periods show a strong impact of AMPAR immobilization solely, prominent when a rule has been recently encoded. 4- In situ examination of the interplay between AMPAR mobility, hippocampal plasticity and spontaneous ripple activities pointed that post-synaptic plasticity at CA3-CA3 recurrent synapses support ripple generation. As crucial results were reproduced using another AMPARM blockade strategy, we propose that after rule encoding, post-synaptic AMPAR mobility at CA3 recurrent synapses support the generation of ripples necessary for rule consolidation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.21.533692v1?rss=1 Authors: Arias-Cavieres, A., Garcia, A. Abstract: Underdeveloped breathing results from premature birth and causes intermittent hypoxia during the early neonatal period. Neonatal intermittent hypoxia (nIH) is a condition linked to the increased risk of neurocognitive deficit later in life. However, the underlying mechanistic consequences nIH-induced neurophysiological changes remains poorly resolved. Here, we investigated the impact of nIH on hippocampal synaptic plasticity and NMDA receptor (NMDAr) expression in neonatal mice. Our findings indicate that nIH induces a pro-oxidant state, leading to an imbalance in NMDAr subunit composition that favors GluN2A over GluN2B expression, and subsequently impairs synaptic plasticity. These consequences persist in adulthood and coincide with deficits in spatial memory. Treatment with the antioxidant, manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), during nIH effectively mitigated both immediate and long-term effects of nIH. However, MnTMPyP treatment post-nIH did not prevent the long-lasting changes in either synaptic plasticity or behavior. Our results underscore the central role of the pro-oxidant state in nIH-mediated neurophysiological and behavioral deficits and importance of stable oxygen homeostasis during early life. These findings suggest that targeting the pro-oxidant state during a discrete window may provide a potential avenue for mitigating long-term neurophysiological and behavioral outcomes when breathing is unstable during early postnatal life. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.19.533284v1?rss=1 Authors: Mongredien, R., Anesio, A., Fernandes, G. J. D., Eagle, A. L., Maldera, S., Pham, C., Vilette, A., Bianchi, P. C., Franco, C., Louis, F., Gruszczynski, C., Betancur, C., Erdozain, A. M., Robison, A. J., Boucard, A. A., Li, D. J., Cruz, F. C., Gautron, S., Heck, N., Vialou, V. Abstract: Drug addiction involves profound modifications of neuronal plasticity in the nucleus accumbens, which may engage various cell types. Here, we report prominent effects of cocaine on calcium signals in astrocytes characterized by in vivo fiber photometry. Astrocyte calcium signals in the nucleus accumbens are sufficient and necessary for the acquisition of cocaine seeking behavior. We identify the astrocyte-secreted matricellular protein hevin as an effector of the action of cocaine and calcium signals on reward and neuronal plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.18.533245v1?rss=1 Authors: Sarkar, S., Gharami, K., Paidi, R. K., Srikumar, B. N., Biswas, S. C. Abstract: Astrocytes respond to any pathological insult to brain including Alzheimer's disease (AD) through 'reactive astrogliosis'. Recently, we demonstrated that tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), a neuroprotective cytokine, is released through reactive astrogliosis early in response to amyloid-{beta} (A{beta}). Here, we show that TIMP-1 has superior mechanism-of-actions on neurons in models of AD. It not only confers neuroprotection against A{beta}-induced apoptosis and autophagy via CD63 receptor but also displays synapse-specific effects that underlie cognitive recovery in AD. We detect diminished levels of TIMP-1 in the hippocampi of 5xFAD mice versus wild-type counterparts. Interestingly, exogenous TIMP-1 injection in this transgenic model ameliorates its cognitive functions, likely by restoring long-term potentiation at hippocampal synapses. We observe BDNF induction and GSK3{beta} inhibition, which may be the key TIMP-1-driven underlying mechanisms at synapses. Thus, we show an astrocyte-origin cytokine-driven mechanism for synaptic and cognitive salvation promising an exciting avenue in AD therapeutic research. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.15.532740v1?rss=1 Authors: Roessler, N., Jungenitz, T., Sigler, A., Bird, A., Mittag, M., Rhee, J., Deller, T., Cuntz, H. J., Brose, N., Schwarzacher, S., Jedlicka, P. Abstract: Dendritic spines are crucial for excitatory synaptic transmission as the size of a spine head correlates with the strength of its synapse. The distribution of spine head sizes follows a lognormal-like distribution with more small spines than large ones. We analysed the impact of synaptic activity and plasticity on the spine size distribution in adult-born hippocampal granule cells from rats with induced homo- and heterosynaptic long-term plasticity in vivo and CA1 pyramidal cells from Munc-13-1-Munc13-2 knockout mice with completely blocked synaptic transmission. Neither induction of extrinsic synaptic plasticity nor the blockage of presynaptic activity degrades the lognormal-like distribution but changes its mean, variance and skewness. The skewed distribution develops early in the life of the neuron. Our findings and their computational modelling support the idea that intrinsic synaptic plasticity is sufficient for the generation, while a combination of intrinsic and extrinsic synaptic plasticity maintains lognormal like distribution of spines. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.27.530317v1?rss=1 Authors: Dell'Orco, M., Weisend, J. E., Perrone-Bizzozero, N. I., Carlson, A. P., Morton, R. A., Linsenbardt, D. N., Shuttleworth, C. W. Abstract: Spreading depolarization (SD) is a slowly propagating wave of profound depolarization that sweeps through cortical tissue. While much emphasis has been placed on the damaging consequences of SD, it is possible that SDs also activate compensatory pathways related to cell survival and plasticity. The present study aimed to provide an unbiased assessment of gene expression changes following SD, as well as novel molecular networks associated with these transcriptional alterations. SD clusters were induced with either focal application of KCl or with optogenetic stimulation in healthy mice, and then 2 hours later cortical RNA was extracted and sequenced. SDs significantly increased the expression of 21 genes - no genes were significantly downregulated. Notable top hits included the immediate early genes FOS, ARC, and JUN, the cell proliferation-related gene DUSP6, the plasticity-related gene HOMER1, and inflammation related genes PTGS2, EGR2, and NR4A1. Pathway analysis identified the recruitment of genes associated with axonogenesis, branching, neuritogenesis, and dendritic growth, as well as inhibition of pathways associated with cell death, apoptosis, and neuronal degeneration. These results identify the induction of plasticity and/or circuit modification as an important consequence of SDs in healthy tissue, as well as specific gene targets and pathways amenable to manipulation in follow up studies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Kick off the new year with Ellen, who tells you all about synaptic transmission in Alzheimer's disease in this episode. You'll hear about 5 papers published in October of 2022 on synaptic transmission, ranging from research on whole brain networks all the way down to individual proteins. -------------------------------------------------------------- To access the numbered bibliography for this episode, click here, or use the link below:https://drive.google.com/file/d/1sIxUDc8NrG6HAXL9ikKCCGx6KgX--ULp/view?usp=share_linkTo access the folder with ALL our bibliographies, follow this link (it will be updated as we publish episodes and process bibliographies), or use the link below:https://drive.google.com/drive/folders/1bzSzkY9ZHzzY8Xhzt0HZfZhRG1Gq_Si-?usp=sharingYou can also find all of our bibliographies on our website: www.amindr.com. --------------------------------------------------------------Follow-up on social media for more updates!Twitter: @AMiNDR_podcastInstagram: @AMiNDR.podcastFacebook: AMiNDR Youtube: AMiNDR PodcastLinkedIn: AMiNDR PodcastEmail: amindrpodcast@gmail.com -------------------------------------------------------------- Please help us spread the word about AMiNDR to your friends, colleagues, and networks! And if you could leave us a rating and/or review on your streaming app of choice (Apple Podcasts, Spotify, or wherever you listen to the podcast), that would be greatly appreciated! It helps us a lot and we thank you in advance for leaving a review! Don't forget to subscribe to hear about new episodes as they come out too. Thank you to our sponsor, the Canadian Consortium of Neurodegeneration in Aging, or CCNA, for their financial support of this podcast. This helps us to stay on the air and bring you high quality episodes. You can find out more about the CCNA on their website: https://ccna-ccnv.ca/. Our team of volunteers works tirelessly each month to bring you every episode of AMiNDR. This episode was scripted, hosted, and edited by Ellen Koch, and reviewed by Anusha Kamesh. The bibliography and wordcloud were created by Lara Onbasi (www.wordart.com). Big thanks to the sorting team for taking on the enormous task of sorting all of the Alzheimer's Disease papers into episodes each month. For October 2022, the sorters were Sarah Louadi, Eden Dubchak, Ben Cornish, Christy Yu, Dana Clausen, Kevin Nishimura, Salodin Al-Achkar, and Elyn Rowe. Also, props to our management team, which includes Sarah Louadi, Ellen Koch, Naila Kuhlmann, Elyn Rowe, Anusha Kamesh, Lara Onbasi, Joseph Liang, and Judy Cheng, for keeping everything running smoothly.Our music is from "Journey of a Neurotransmitter" by musician and fellow neuroscientist Anusha Kamesh; you can find the original piece and her other music on soundcloud under Anusha Kamesh or on her YouTube channel, AKMusic. https://www.youtube.com/channel/UCMH7chrAdtCUZuGia16FR4w -------------------------------------------------------------- If you are interested in joining the team, send us your CV by email. We are specifically looking for help with sorting abstracts by topic, abstract summaries and hosting, audio editing, creating bibliographies, and outreach/marketing. However, if you are interested in helping in other ways, don't hesitate to apply anyways. --------------------------------------------------------------*About AMiNDR: * Learn more about this project and the team behind it by listening to our first episode: "Welcome to AMiNDR!"
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.21.521348v1?rss=1 Authors: Aidil-Carvalho, F., Caulino-Rocha, A., Ribeiro, J. A., Cunha-Reis, D. Abstract: Novelty influences hippocampal-dependent memory through metaplasticity, i.e., experience-dependent adaptations in synaptic plasticity. In this respect, mismatch novelty is known to activate the hippocampal CA1 area in humans and to enhance rat hippocampal-dependent learning and exploration. Mismatch novelty training (NT) by varying spatial configuration of objects in a known environment, enhances rat hippocampal synaptic plasticity. Prefrontal cortex GABAergic projections targeting hippocampal VIP interneurons promote exploration. Since VIP, acting on VPAC1 receptors, restrains both hippocampal LTP and depotentiation by modulating disinhibition we now investigated the impact of NT on VPAC1 receptor modulation of hippocampal synaptic plasticity. NT enhanced both CA1 hippocampal long-term potentiation (LTP) and depotentiation. Blockade of VIP VPAC1 receptors with PG 97-269 (100nM) enhanced both LTP and depotentiation in naiuml;ve animals but was much less effective in enhancing LTP and depotentiation in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). Modulation of depotentiation by endogenous VIP was absent in animals exposed to a fixed configuration of objects (FT) or in HT animals. HT and FT animals, but not NT; showed mildly enhanced synaptic VPAC1 receptor expression. Altogether this suggests that NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons. Also, upregulation of VIP VPAC1 receptors maintains VIP control of LTP in FT and HT rats, the absence of this in NT rats leading to enhanced LTP but not influencing depotentiation. This may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.04.519021v1?rss=1 Authors: Gil, B., Rose, J., Demurtas, D., Mancini, G.-F., Sordet-Dessimoz, J., Sorrentino, V., Rudinskiy, N., Frosh, M. P., Hyman, B. T., Moniatte, M., Spires-Jones, T. L., Herron, C. E., Schmid, A. W. Abstract: In Alzheimer's disease (AD), Amyloid-beta (A{beta}) oligomers are considered an appealing therapeutic- and diagnostic target. However, to date, the molecular mechanisms associated with the pathological accumulation or structure of A{beta} oligomers remains an enigma to the scientific community. Here we demonstrate the strong seeding properties of unique A{beta} fragment signatures and show that the truncated A{beta}peptides of residues A{beta}1-23, A{beta}1-24 and A{beta}1-25, rapidly seed to form small, SDS-PAGE stable assemblies of ~5kDa to ~14kDa molecular mass range. Mass spectrometry analysis of SDS-PAGE fractionated and gel extracted oligomers revealed that the truncated A{beta} isoforms of residues 1-23 to 1-25 form stable entities with low molecular weight (LMW) oligomers, which strongly resemble the regularly reported A{beta} entities of putative dimeric or trimeric assemblies found in human post-mortem AD and Tg mouse brain extracts. Furthermore, electrophysiological recordings in the mouse hippocampus indicate that LMW A{beta} assemblies formed by fragments A{beta}1-23 to A{beta}1-25 significantly impair long-term-potentiation (LTP) in the absence of full-length A{beta}1-42. Extensive antibody screening highlights the important observation, that the LMW A{beta} assemblies formed by these truncated A{beta} peptides escape immuno-detection using conventional, conformation specific antibodies but, more importantly, the clinical antibody aducanumab. Our novel findings suggest that there are new A{beta} target loopholes which can be exploited for the development of therapeutic antibodies with binding properties against stable target hotspots present in A{beta} oligomers. We provide here a first example of a new class of monoclonal antibody with unique binding properties against LMW A{beta} oligomers, in the absence of binding to large fibrillar A{beta} assemblies, or dense amyloid plaques. Our research supports a novel, unparalleled approach for targeting early, pathological A{beta} species during the insidious phase of AD and prior to the appearance of large oligomeric or protofibrilar assemblies. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.30.518536v1?rss=1 Authors: Gala, D. S., Lee, J. Y., Kiourlappou, M. S., Titlow, J. S., Teodoro, R. O., Davis, I. Abstract: The polarization of cells often involves the transport of specific mRNAs and their localized translation in distal projections. Neurons and glia both contain long cytoplasmic processes with important functions. While mRNA localization has been studied extensively in neurons, little is known in glia, especially in intact nervous systems. Here, we predicted 1700 localized Drosophila glial transcripts by extrapolating from our meta-analysis of 8 existing studies characterizing the localized transcriptomes and translatomes of synaptically-associated mammalian glia. We tested these predictions in glia of the neuromuscular junction of Drosophila larvae and found that localization to vertebrate glia is a strong predictor of mRNA localization of the high confidence Drosophila homologues. We further showed that some of these localized transcripts are required in glia for plasticity of neuromuscular junction synapses. We conclude that peripheral glial mRNA localization is a common and conserved phenomenon and propose that it is likely to be functionally important. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.15.516556v1?rss=1 Authors: Pariz, A., Trotter, D., Hutt, A., Lefebvre, J. Abstract: Transcranial alternating current stimulation (tACS) represents a promising non-invasive treatment for an increasingly wide range of neurological and neuropsychiatric disorders. The ability to use periodically oscillating electric fields to non-invasively engage neural dynamics opens up the possibility of recruiting synaptic plasticity and to modulate brain function. However, despite consistent reports about tACS clinical effectiveness, strong state-dependence combined with the ubiquitous heterogeneity of cortical networks collectively results in high outcome variability. Introducing variations in intrinsic neuronal timescales, we explored how such heterogeneity influences stimulation-induced change in synaptic connectivity. We examined how spike timing dependent plasticity, at the level of cells, intra- and inter-laminar cortical networks, can be selectively and preferentially engaged by periodic stimulation. Using computational simulations informed by human experimental data, we analyzed cortical circuits comprised of multiple cell-types, alongside superficial multi-layered networks expressing distinct layer-specific timescales. Our results show that mismatch in neuronal timescales within and/or between cells - and the resulting variability in excitability, temporal integration properties and frequency tuning - enables selective and directional control on synaptic connectivity by tACS. Our work provides new vistas on how to recruit neural heterogeneity to guide brain plasticity using non-invasive stimulation paradigms. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.01.514765v1?rss=1 Authors: Lefevre, E. M., Gauthier, E. A., Bystrom, L. L., Scheunemann, J., Rothwell, P. E. Abstract: Opioid exposure and withdrawal both cause adaptations in brain circuits that may contribute to abuse liability. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological impact. In this study, we compared cellular and synaptic adaptations in the nucleus accumbens shell caused by morphine exposure that was either continuous, or interrupted by daily bouts of naloxone-precipitated withdrawal. At the behavioral level, continuous morphine administration caused psychomotor tolerance, which was reversed when the continuity of morphine action was interrupted by naloxone-precipitated withdrawal. Using ex vivo slice electrophysiology in female and male mice, we investigated how these patterns of morphine administration altered intrinsic excitability and synaptic plasticity of medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. We found that morphine-evoked adaptations at excitatory synapses were predominately conserved between patterns of administration, but there were divergent effects on inhibitory synapses and the subsequent balance between excitatory and inhibitory synaptic input. Overall, our data suggest that continuous morphine administration produces adaptations that dampen the output of D1-MSNs, which are canonically thought to promote reward-related behaviors. Interruption of otherwise continuous morphine exposure does not dampen D1-MSN functional output to the same extent, which may enhance behavioral responses to subsequent opioid exposure. Our findings support the hypothesis that maintaining continuity of opioid administration could be an effective therapeutic strategy to minimize the vulnerability to opioid use disorders. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.28.514318v1?rss=1 Authors: Zhou, S., Buonomano, D. V. Abstract: Neuromodulators such as dopamine have been shown to modulate short-term synaptic plasticity (STP). Here we propose that the neuromodulation of STP provides a general mechanism to scale neural dynamics and motor outputs in time and space. We trained RNNs that incorporated STP to produce complex motor trajectories-handwritten digits-with different temporal (speed) and spatial (size) scales. The learned dynamics underwent temporal and spatial scaling when higher synaptic release probabilities corresponded to higher speed/size. Neuromodulation of STP enhanced temporal or spatial generalization compared to weight modulation alone. The model accounted for the data of two experimental studies involving flexible sensorimotor timing. Our results address a long-standing debate regarding the role of dopamine in timing and predict novel mechanisms by which dopamine may slow down neural dynamics and thus slow 'clock' speed. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.25.513721v1?rss=1 Authors: Liu, R., Zhang, Y., smolen, p. d., Byrne, J. d. Abstract: Mechanisms of specific memory deficits associated with Rett syndrome are poorly understood, at least in part because mutations of MECP2 have confounding effects on nervous system development and basal synaptic transmission. To mitigate such empirical uncertainties, this study exploited technical advantages of the Aplysia sensorimotor synapse to examine the potential role of MeCP2 in long-term synaptic plasticity. The results indicate MeCP2 may act as an inhibitory constraint on gene expression required for formation as well as maintenance of plasticity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Join Caroline for Part 3 of our “What is Aging?” series covering the nervous system. In this episode we give an overview of what is happening at the cellular level inside the nervous system as we age and the implications for learning and memory, as well as neurodegenerative conditions like Alzheimer's disease and Parkinson's disease. Episodes on Aging: Ep 32 - Aging Bones & Joints Ep 33 - Aging Muscles Episodes on Brain Health: Ep 28 - Integrative Brain Health with Dr. Andrew Wong Ep 22- Communication and Care Partners with Abbe Simon Ep 16 - Exercise for Your Heart and Brain with Laura Mesches Ep 6 - Parkinson's Practicalities with Nicole Reynolds Ep 2 - Dignity in Dementia Care with Anne Stankiewicz Ep 1 - Memory and Communication Across the Lifespan with Alicia White Further Reading: Todorova, V., & Blokland, A. (2016). Mitochondria and Synaptic Plasticity in the Mature and Aging Nervous System. Current Neuropharmacology, 15(1), 166–173. https://doi.org/10.2174/1570159x14666160414111821 Work with Caroline: Schedule an intro call: https://morrisclinicpt.janeapp.com https://carolinemorris.com
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.05.510980v1?rss=1 Authors: Barron, J. C., Nafar, F., Parsons, M. P. Abstract: Huntingtin (HTT), an exceptionally large protein with hundreds of interacting partners within the central nervous system, has been extensively studied due to its role in Huntington's disease (HD) pathology. HD is a monogenic disorder caused by a polyglutamine repeat expansion in the HTT gene, which results in the production of a pathogenic mutant huntingtin (mHTT) protein, and toxic effects of this mutant protein in the context of HD have been well-established. Less-established, however, is the role of wild type HTT (wtHTT) in the adult brain, particularly in areas outside the corticostriatal pathway. wtHTT has previously been suggested to play a vital role in cellular functions that promote synapse homeostasis, such as fast axonal transport of synaptic cargo, vesicle replenishment and receptor localization and stability. Synaptic dysfunction precedes and predicts cell death in many neurodegenerative diseases including HD (termed synaptopathies) and whether proper synaptic transmission can be maintained without wtHTT in extrastriatal brain areas such as the hippocampus remains unknown. Consequences of wtHTT reduction in the adult brain are of particular importance as clinical trials for many non-selective HTT-lowering therapies for HD are underway, which are unable to distinguish between mHTT and wtHTT, and therefore reduce levels of both proteins. We investigated the consequences of wtHTT loss of function in the CA3-CA1 pathway of the adult hippocampus using a conditional knockout mouse model and found that 1-2 month deletion of wtHTT in excitatory hippocampal neurons inhibits post-tetanic potentiation and completely abolishes NMDA receptor-dependent long-term potentiation in these animals. These data reveal a novel role of wtHTT as an essential regulator of short- and long-term plasticity in the adult hippocampus. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.05.510966v1?rss=1 Authors: Hurley, E. P., Mukherjee, B., Fang, L., Barnes, J. R., Nafar, F., Hirasawa, M., Parsons, M. P. Abstract: N-methyl-D-aspartate receptors (NMDARs) assemble as functionally diverse heterotetramers. Incorporation of the GluN3A subunit into NMDARs alters conventional NMDAR properties by reducing both magnesium sensitivity and calcium permeability. GluN1 together with GluN3A can also form functional receptors that lack a glutamate binding site and instead serve as excitatory glycine receptors (eGlyRs). GluN3A expression is high in early development but naturally declines to low levels in most brain regions by adulthood. Interestingly, GluN3A expression remains elevated in the CA1 of the adult ventral hippocampus (VH), but not in the dorsal hippocampus (DH). The DH and VH are now well-understood to play very different functional roles, with the DH being primarily involved in cognitive functions and the VH in emotional processing. Why GluN3A persists in the adult VH, and the impact its presence has on glutamatergic neurotransmission in the VH is currently unknown. Here, we show that GluN3A remains elevated both at synaptic and extrasynaptic locations in the adult VH, assembling as GluN1/GluN2/GluN3A NMDARs with reduced magnesium sensitivity, as well as GluN1/GluN3A eGlyRs. By comparing various synaptic properties in the DH and VH of wild-type (WT) and GluN3A knockout (KO) mice, we demonstrate that GluN3A persistence in the VH attenuates glutamate release, limits postsynaptic calcium influx through NMDARs, and reduces the magnitude of NMDAR-dependent long-term potentiation. In comparison, GluN3A KO had relatively little effect on these same properties in the DH. In all, our data demonstrate that GluN3A persistence in the VH represents a key modulator of VH excitability and therefore may play a central role in emotional processing. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.13.507796v1?rss=1 Authors: Lankarany, M., Azzalini, L. J. Abstract: Neuromorphic chips are well-suited for the exploration of neuronal dynamics in (near) real-time. In order to port existing research onto these chips, relevant models of neuronal and synaptic dynamics first need to be supported by their respective development environments and validated against existing simulator backends. At the time of writing, support for short-term synaptic plasticity on neuromorphic hardware is scarce. This technical paper proposes an implementation of dynamic synapses for the SpiNNaker development environment based on the popular synaptic plasticity model by Tsodyks and Markram (TM). This extension is undertaken in the context of existing research on neuromodulation and the study of deep brain stimulation (DBS) effects on singular-neuron responses. The implementation of the TM synapse is first detailed and then, simulated for various response types. Its role in studies of DBS effect on postsynaptic responses is also reviewed. Finally, given the real-time capabilities offered by the hardware, we provide some insights to lay the groundwork for future explorations of closed-loop DBS on neuromorphic chips. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Dion Dickman, associate professor of neuroscience and gerontology, joins George Shannon to discuss how the nervous system processes and stabilizes the transfer of information in healthy brains, aging brains and after injury or disease. Quotes from the episode: On synaptic plasticity: “Synapses are essential, fundamental units of nervous system function and plasticity is this remarkable ability to change. And throughout early development into maturation and even into old age, synapses just have this amazing resilience to change and adapt to different situations and injury disease, things like that. So synaptic plasticity is really the essence of what it means to grow and mature and change throughout life. Things like learning and memory all depend on changes in synaptic function and structure and it's really a key area of research for many of us.” On challenges to maintaining nervous system stability: “You can imagine in the incredibly complex environment of your brain, where neurons are making synapses with thousands of other neurons, that itself is a big challenge to maintain stability. Sometimes I'm kind of amazed that we don't walk around like raving lunatics half the time and our brains remain stable. When you think of disorders of excitability or stability, things like seizures and various forms of defects in cognition ultimately come down to not being able to stabilize or maintain your neural circuit function. And this really just comes down to normal development that all of your nervous system has to stay stable and your synapses are the key substrates to maintain stability.” On the aging brain: “.. a lot of studies are showing is that this cognitive decline that happens in aging really is ultimately due some sort of a maladaptive reduction in plasticity. And it's kind of amazing, but, young humans, our brains are remarkably plastic and resilient, and that resiliency and plasticity seems to degrade over time and into old age… We think as old age happens .. people's memories start to lapse, even in the absence of any disease, they're not quite as sharp. We think this all ultimately comes down to some limitations imposed on neuroplasticity and that's a major area of the research. On studying diseases like schizophrenia, which cannot be seen in brain imaging: “There are no good biomarkers for neuropsychiatric diseases like schizophrenia and bipolar and things like that. So, there are basically two ways to study these kinds of diseases. One is through behavior where you try to get animals to model behaviors that mimic neuropsychiatric diseases. There's some good work happening rodent systems. Although I find it to be honest, very difficult to know whether a mouse is showing the defect in social interaction, for example, that are characteristic of autism or schizophrenia for that matter. So the alternative instead is not to actually model the disease in drosophila or mice, but to take humans in which we can mine their genetics to find genes highly associated with the disease in humans and find out what the fundamental function of these genes are. And that's kind of the strategy that we take. So we found about 30 genes now that when mutated in drosophila give rise to defects in this process of homeostatic plasticity at synapses, and the vast majority of these genes have links to human diseases that give rise to neuropsychiatric diseases like autism spectrum disorder, schizophrenia, seizure disorders and, bipolar disorder as well. And so I think by understanding the fundamental functions of individual genes, we can extrapolate what might be happening in humans when those genes aren't functioning properly.” On the importance of sleep: “…one of the most fascinating questions in neuroscience, or really science more generally is what is the function of sleep? What is the essential function of sleep and what role does synaptic homeostasis and disease play a role in sleep behavior? So, it's quite interesting that almost every neuropsychiatric disease has a sleep disorder associated with it. That's already very interesting. If you look at schizophrenics, their sleep patterns tend to be very fragmented. Whereas people with depression, chronic depression seem to sleep too much, much more than is needed and many neurodegenerative diseases of old age like Parkinson's, and Alzheimer's one of the earliest predictors of these are sleep dysfunction at earlier stages and there's also many studies that have shown that if you treat the sleep dysfunction, you can improve the symptoms of neuropsychiatric disorders. A schizophrenic, for example, might get if you improve their sleep, their symptoms, cognitive symptoms seem to improve children with autism spectrum disorder have, big defects in sleep behavior during development. And it's thought that if you treat the sleep defect, you can improve the phenotypes of autism. So a lot of research seems to be showing that synaptic homeostasis and plasticity and sleep behavior and disease all share really important and synergistic links between them. And I think that really is the major challenge for the future is to understand what happens to synapses during sleep. What happens to synapses during various neuropsychiatric diseases and can this intimate relationship between sleep and, and synaptic plasticity be targeted as a way to improve and treat psychiatric and neurodegenerative diseases.” On bringing a multidisciplinary approach to research: This is a big advantage, I think of especially working at USC, in, you know, straddling different schools like Dornsife and gerontology and really being able to throw everything we can in our toolkit at a question or a problem. So, our lab is a drosophila genetics lab. We do neurogenetics. But we do electrophysiology to understand how synapses function we do basic imaging to see synaptic structures and how they work. But we also do a lot of super resolution imaging. Now we've got a super resolution microscope that we've recently purchased that allows us to look at the nano architecture of synapses and how they might change during defects and plasticity and disease. And finally, we're doing things like calcium and voltage imaging to really see the dynamics of how, you know, visualize plasticity happening in real time or dysfunction happening as they go on. So I think having a large toolkit to throw everything we can at a question really lets you see the same problem from many different perspectives. On the value of basic scientific research: “Science is for me a curiosity driven process. It's great that there are ramifications to disease and health and humans, but what initially inspired me was just to understand how does nature work and how does the nervous system work. And so I want to just say supporting basic research, basic science, even if it doesn't have any direct implications on disease right away, I think is really important as part of scholarship, as part of what we at the mission of our university, but also just as our world. I think to study basic processes and just understand how nature works and then the applications of them with all evolve. You know CRISPR CAS9, as many of you have probably heard about, all came from basic research and now it is going to revolutionize health and disease.”
References Dr Guerra's notes,concepts and ideas Sci Signal. 2016 Aug 23; 9(442): ra83. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
References Dr Guerra's notes Sci Signal. 2016 Aug 23; 9(442): ra83 Front. Pharmacol., 24 April 2019 --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message
Walking is a brilliant form of exercise but it's often overlooked in favour of running or yoga or HIIT workouts. Because we are exercise sloths and busy women, we're always looking for quick and easy ways to get moving. If you're trying to get fit and healthy, walking is one of the most accessible types of exercise you can do. Gab and Sarah look at some good quality research which shows why walking is really, really good for you. Don't forget to subscribe to the Women Like You newsletter. To be added to the mailing list, email womenlikeyoupodcast@gmail.com WLY resources and recommendations: Sarah's Burpees for Boobs Sydney Breast Cancer Foundation fundraiser Walking for hypertension Association of Step Volume and Intensity With All-Cause Mortality in Older Women Kathy Smith power walking audio workout Waking Up with Sam Harris Heavyweight podcast WLY Spotify playlist The Women Like You podcast is recorded on the lands of the Gadigal people of the Eora nation. We pay our respects to elders past, present and emerging. We acknowledge Aboriginal and Torres Strait Islander peoples as the First Australians and Traditional Custodians of the land where we live, work, and exercise. See omnystudio.com/listener for privacy information.
Have you ever tried Pilates? It's a popular form of exercise that was developed by Joseph Pilates in the early 20th century. It's now a worldwide fitness trend and it's often used as a form of rehabilitation for lower back pain or injury, and recovery after childbirth. Gab and Sarah look at what Pilates actually involves and if it lives up to the hype. Plus, another batshit crazy fitness trend, this time involving Kate Hudson and a bag full of water. Don't forget to subscribe to the Women Like You newsletter. To be added to the mailing list, email womenlikeyoupodcast@gmail.com WLY resources and recommendations: Cochrane Library Pilates for low back pain Jessica Valant - Gentle Pilates 15 Minute Pilates for Beginners Workout WLY Spotify playlist The Women Like You podcast is recorded on the lands of the Gadigal people of the Eora nation. We pay our respects to elders past, present and emerging. We acknowledge Aboriginal and Torres Strait Islander peoples as the First Australians and Traditional Custodians of the land where we live, work, and exercise. See omnystudio.com/listener for privacy information.
How many times have you set yourself a big fitness goal? Did you achieve it? Research shows that having really specific and fixed goals can actually be a deterrent rather than a motivator. In recent years there's been a shift away from the traditional method of goal-setting known as SMART goals (specific, measurable, achievable, realistic and timebound); towards a more flexible approach. Gab and Sarah explain the idea behind ‘open goals', and how this is proving to be a more effective way of achieving a fitness target. You'll also hear about the world record for planking, and a review of Maddie Lymburner's Low Impact Full Body HIIT workout. Don't forget to subscribe to the Women Like You newsletter. To be added to the mailing list, email womenlikeyoupodcast@gmail.com WLY resources and recommendations: ABC Try setting an open goal for your New Year's resolution if you want to exercise more MadFit Low Impact FULL BODY HIIT Workout (No Equipment + No Jumping) Yoga With Adriene Wind Down Yoga (12 minute bedtime yoga) WLY Spotify playlist The Women Like You podcast is recorded on the lands of the Gadigal people of the Eora nation. We pay our respects to elders past, present and emerging. We acknowledge Aboriginal and Torres Strait Islander peoples as the First Australians and Traditional Custodians of the land where we live, work, and exercise. See omnystudio.com/listener for privacy information.
No matter how hard you try, it can often feel like your fitness isn't improving. It's so disappointing when you've been doing the same workouts over and over and you don't see any progress in your strength, or number of reps, or cardiovascular fitness. Even when you've been consistent with your exercise, sometimes it feels like you've hit a wall and you can't get past it. So what do you do when your progress has stalled? Gab and Sarah explain how to reframe the way you measure progress, and look for the many ways you are making headway (even when it doesn't feel like it). Don't forget to subscribe to the Women Like You newsletter. To be added to the mailing list, email womenlikeyoupodcast@gmail.com WLY resources and recommendations: Sports Bras Direct Yoga With Adriene Morning Yoga Flow (22mins) Nike Run Club ‘Don't Wanna Run Run' WLY Spotify playlist Over Ear Earbuds (example only - we have not tried this particular brand) MadFit low Impact FULL BODY HIIT Workout (No Equipment + No Jumping) The Women Like You podcast is recorded on the lands of the Gadigal people of the Eora nation. We pay our respects to elders past, present and emerging. We acknowledge Aboriginal and Torres Strait Islander peoples as the First Australians and Traditional Custodians of the land where we live, work, and exercise. See omnystudio.com/listener for privacy information.
This episode we're talking endocannabinoids and sports bras (the two are not related!). For years it was thought that the “runner's high” was due to the release of endorphins. Endorphins are chemicals that are produced by the body to relieve stress and pain, and they work on the opioid receptors in the brain (the same receptors that opiate drugs like morphine act upon). An increasing body of evidence suggests that this so-called “runner's high” is notdue to the release of endorphins but is instead due to the release of another type of neurochemical called endocannabinoids. And yes, the word endocannabinoid sounds a lot like the word cannabis, and in the same way that endorphins act upon the opiate receptors in the brain, endocannabinoids act upon the same cannabinoid pathways as cannabis. Sarah explains why it's theoretically possible to get a little “high” on exercise, and Gab has some sports bra recommendations for you to check out. Don't forget to subscribe to the Women Like You newsletter. To be added to the mailing list, email womenlikeyoupodcast@gmail.com WLY resources and recommendations: Neuromodulation of Aerobic Exercise—A ReviewSerum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder Sports Bras Direct Bra fitting guide Yoga With Adriene Morning Yoga Flow (22mins) Nike Run Club ‘Don't Wanna Run Run' WLY Spotify playlist The Women Like You podcast is recorded on the lands of the Gadigal people of the Eora nation. We pay our respects to elders past, present and emerging. We acknowledge Aboriginal and Torres Strait Islander peoples as the First Australians and Traditional Custodians of the land where we live, work, and exercise. See omnystudio.com/listener for privacy information.
Ellen kicks off the May 2021 series with 20 papers all about synaptic transmission in Alzheimer's Disease. This includes topics like synaptic plasticity, neurotransmitters like acetylcholine, dopamine, and serotonin and how they're involved in AD, growth factors, morphological changes, and much more! Enjoy the show! Sections in this episode:Neurogenesis (5:11)Synaptic Plasticity (8:46)Neurotransmitter Signaling (18:26)Excitation/Inhibition Balance (28.07)Growth Factors (32:16)Morphological & Anatomical Changes (35:46)-------------------------------------------------------------- PLEASE FILL OUR SURVEY TO HELP US IMPROVE OUR PODCAST, AND ENTER A DRAW FOR A $30 GIFT CARD. Link if you prefer to copy/paste: https://amindr.hostedincanadasurveys.ca/417377?lang=enREGARDLESS OF THE DRAW, YOU WILL ALSO HAVE OUR ENDLESS GRATITUDE & THE SATISFACTION OF KNOWING YOU CONTRIBUTED TO THE BETTERMENT OF THE WORLD.-------------------------------------------------------------- Find the bibliography for this episode here. To access the folder with all the bibliographies for 2021 so far, follow this link (it will be updated as we publish episodes and process bibliographies), or click the following link below:https://drive.google.com/drive/folders/1N1zx_itPkCDNYE1yFGZzQxDDR-NiRx3p?usp=sharingYou can also join our mailing list to receive a newsletter by filling this form. Or tweet at us: @AMiNDR_podcast --------------------------------------------------------------Follow-up on social media for more updates!Facebook: AMiNDR Twitter: @AMiNDR_podcastInstagram: @AMiNDR.podcastYoutube: AMiNDR PodcastLinkedIn: AMiNDR PodcastIf you have any questions or concerns, do not hesitate to contact us at: amindrpodcast@gmail.com -------------------------------------------------------------- Please help us by spreading the word about AMiNDR to your friends, colleagues, and networks! Another way you can help us reach more researchers is by leaving us a review on Apple Podcasts. We would like to thank our amazing team for all of the work that goes into every episode of AMiNDR. Today's episode was scripted, hosted, and edited by Ellen Koch, and reviewed by Anusha Kamesh. The bibliography was created by Sarah Louadi who also generated the wordcloud onwww.wordart.com. Big thanks to the sorting team for sorting all the papers published in May into themes for our episodes: Jacques Ferreira, Elyn Rowe, Christy Yu, Nicole Corso, Ellen Koch, and Naila Kuhlmann. Also, props to our management team, which includes Sarah Louadi, Ellen Koch, Naila Kuhlmann, Elyn Rowe, Anusha Kamesh, and Jacques Ferreira, for keeping everything running smoothly.Our music is from "Journey of a Neurotransmitter" by musician and fellow neuroscientist Anusha Kamesh; you can find the original piece and her other music on soundcloud under Anusha Kamesh or on her YouTube channel, AKMusic. https://www.youtube.com/channel/UCMH7chrAdtCUZuGia16FR4w -------------------------------------------------------------- If you are interested in joining the team, send us your CV by email. We are specifically looking for help with sorting abstracts by topic, abstract summaries and hosting, creating bibliographies, and promotions. However, if you are interested in helping in other ways, don't hesitate to apply anyways. --------------------------------------------------------------*About AMiNDR: * Learn more about this project and the team behind it by listening to our first episode: "Welcome to AMiNDR!"
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.352310v1?rss=1 Authors: Van Hook, M. J., Monaco, C., Smith, J. Abstract: Homeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma - the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.20.346858v1?rss=1 Authors: Mendoza, M. B., Gutierrez, S., Ortiz, R., Moreno, D. F., Dermit, M., Dodel, M., Rebollo, E., Bosch, M., Mardakheh, F. K., Gallego, C. Abstract: Synaptic plasticity involves structural modifications in dendritic spines. Increasing evidence suggests that structural plasticity is modulated by local protein synthesis and actin remodeling in a synapsis-specific manner. However, the precise molecular mechanisms connecting synaptic stimulation to these processes in dendritic spines are still unclear. In the present study, we demonstrate that the configuration of phosphorylation sites in eEF1A2, an essential translation elongation factor in neurons, is a key modulator of structural plasticity in dendritic spines. A mutant that cannot be phosphorylated stimulates translation but reduces actin dynamics and spine density. By contrast, the phosphomimetic variant loosens its association with F-actin and becomes inactive as a translation elongation factor. Metabotropic glutamate receptor signaling triggers a transient dissociation of eEF1A2 from its GEF protein in dendritic spines, in a phospho-dependent manner. We propose that eEF1A2 establishes a crosstalk mechanism that coordinates local translation and actin dynamics during spine remodeling Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.19.344564v1?rss=1 Authors: Oliveira, M. M., Lourenco, M. V., Longo, F., Kasica, N. P., Yang, W., Ureta, G., Ferreira, D. D. P., Mendonca, P. H. J., Bernales, S., Ma, T., De Felice, F. G., Klann, E., Ferreira, S. T. Abstract: Neuronal protein synthesis is essential for long-term memory consolidation. Conversely, dysregulation of protein synthesis has been implicated in a number o neurodegenerative disorders, including Alzheimer's disease (AD). Several types of cellular stress trigger the activation of protein kinases that converge on the phosphorylation of eukaryotic translation initiation facor 2 (eIF2-P). This leads to attenuation of cap-dependent mRNA translation, a component of the integrated stress response (ISR). We show that AD brains exhibit increased eIF2-P and reduced eIF2B, key components of the eIF2 translation initiation complex. We further demonstrate that attenuating the ISR wit the small molecule compound ISRIB (ISR inhibitor) rescues hippocampal protein synthesis and corrects impaired synaptic plasticity and memory in mouse models of AD. Our findings suggest that attenuating eIF2-P-mediated translational inhibition may comprise an effective approach to alleviate cognitive decline in AD. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.16.336065v1?rss=1 Authors: Lenz, M., Eichler, A., Kruse, P., Strehl, A., Rodriguez-Rozada, S., Goren, I., Yogev, N., Frank, S., Waisman, A., Deller, T., Jung, S., Maggio, N., Vlachos, A. Abstract: Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNF) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNF, IL6, IL1{beta}, and IFN{gamma} and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.13.337188v1?rss=1 Authors: Guerreiro, I., Gu, Z., Yakel, J., Gutkin, B. Abstract: Hippocampal synaptic plasticity, particularly in the Schaffer collateral (SC) to CA1 pyramidal excitatory transmission, is considered as the cellular mechanism underlying learning. The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Our recent experiments showed that repeated cholinergic activation of 7 nACh receptors expressed in oriens-lacunosum-moleculare (OLM2) interneurons could induce LTP in SC-CA1 synapses, likely through disinhibition by inhibiting stratum radiatum (s.r.) interneurons that provide feedforward inhibition onto CA1 pyramidal neurons, revealing a potential mechanism for local interneurons to regulate SC-CA1 synaptic plasticity. Here, we pair in vitro studies with biophysically-based modeling to uncover the mechanisms through which cholinergic-activated GABAergic interneurons can disinhibit CA1 pyramidal cells, and how repeated disinhibition modulates hippocampal plasticity at the excitatory synapses. We found that 7 nAChR activation increases OLM activity. OLM neurons, in turn inhibit the fast-spiking interneurons that provide feedforward inhibition onto CA1 pyramidal neurons. This disinhibition, paired with tightly timed SC stimulation, can induce potentiation at the excitatory synapses of CA1 pyramidal neurons. Our work further describes the pairing of disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity. Disinhibition of the excitatory synapses, paired with SC stimulation, leads to increased NMDAR activation and intracellular calcium concentration sufficient to upregulate AMPAR permeability and potentiate the synapse. Repeated paired disinhibition of the excitatory synapse leads to larger and longer lasting increases of the AMPAR permeability. Our study thus provides a novel mechanism for inhibitory interneurons to directly modify glutamatergic synaptic plasticity. In particular, we show how cholinergic action on OLM interneurons can down-regulate the GABAergic signaling onto CA1 pyramidal cells, and how this shapes local plasticity rules. We identify paired disinhibition with SC stimulation as a general mechanism for the induction of hippocampal synaptic plasticity. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.24.312686v1?rss=1 Authors: Canto-Bustos, M., Friason, F. K. E., Bassi, C., Oswald, A.-M. M. Abstract: Inhibitory microcircuits play an essential role in regulating cortical responses to sensory stimuli. Interneurons that inhibit dendritic or somatic integration in pyramidal neurons are gatekeepers for neural activity, synaptic plasticity and the formation of sensory representations. Conversely, interneurons that specifically inhibit other interneurons can open gates through disinhibition. In the rodent piriform cortex, relief of dendritic inhibition permits long-term potentiation (LTP) of the recurrent synapses between pyramidal neurons (PNs) thought to underlie ensemble odor representations. We used an optogenetic approach to identify the inhibitory interneurons and disinhibitory circuits that regulate LTP. We focused on three prominent inhibitory neuron classes- somatostatin (SST), parvalbumin (PV), and vasoactive intestinal polypeptide (VIP) interneurons. We find that VIP interneurons inhibit SST interneurons and promote LTP through subthreshold dendritic disinhibition. Alternatively, suppression of PV-interneuron inhibition promotes LTP but requires suprathreshold spike activity. Thus, we have identified two disinhibitory mechanisms to regulate synaptic plasticity during olfactory processing. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.14.286765v1?rss=1 Authors: Han, J.-K., Kwon, S.-H., Kim, Y. G., Choi, J., Kim, J.-I., Lee, Y.-S., Ye, S.-K., Kim, S. J. Abstract: Emotional memory processing, such as fear memory, engages a large neuronal network of brain regions including the cerebellum. However, the molecular and cellular mechanisms of the cerebellar cortex modulating the fear memory network is largely unknown. Here, we illustrate a novel mechanism by which synaptic signaling in cerebellar Purkinje cells (PCs) via STAT3 regulates long-term fear memory. Firstly, we generated PC-specific STAT3 knockout (STAT3PKO) mice. Transcriptome analyses revealed that STAT3 deletion results in transcriptional changes that lead to an increase in the expression of glutamate receptors. The amplitude of AMPA receptor-mediated excitatory postsynaptic currents at parallel fiber to PC synapses was larger in STAT3PKO mice than in wild-type littermates. Conditioning at the parallel fiber induced long-term depression of parallel fiber-PC synapses in STAT3PKO mice while the same manipulation induced long-term potentiation in wild-type littermates. Interestingly, STAT3PKO mice showed an aberrantly enhanced long-term fear memory. Neuronal activity in fear-related regions increased in fear-conditioned STAT3PKO mice. Our data suggest that STAT3-dependent molecular regulation in PCs is indispensable for proper expression of fear memory processing. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.08.287714v1?rss=1 Authors: Brochard, J., Daunizeau, J. Abstract: Computational investigations of learning and decision making suggest that systematic deviations to adaptive behavior may be the incidental outcome of biological constraints imposed on neural information processing. In particular, recent studies indicate that range adaptation, i.e., the mechanism by which neurons dynamically tune their output firing properties to match the changing statistics of their inputs, may drive plastic changes in the brain's decision system that induce systematic deviations to rationality. Here, we ask whether behaviorally-relevant neural information processing may be distorted by other incidental, hard-wired, biological constraints, in particular: Hebbian plasticity. One of our main contributions is to propose a simple computational method for identifying (and comparing) the neural signature of such biological mechanisms or constraints. Using ANNs (i.e., artificial neural network models) and RSA (i.e., representational similarity analysis), we compare the neural signatures of two types of hard-wired biological mechanisms/constraints: namely, range adaptation and Hebbian plasticity. We apply the approach to two different open fMRI datasets acquired when people make decisions under risk. In both cases, we show that although peoples' apparent indifferent choices are well explained by biologically-constrained ANNs, choice data alone does not discriminate between range adaptation and Hebbian plasticity. However, RSA shows that neural activity patterns in bilateral Striatum and Amygdala are more compatible with Hebbian plasticity. Finally, the strength of evidence for Hebbian plasticity in these structures predicts inter-individual differences in choice inconsistency. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.04.267104v1?rss=1 Authors: Lenz, M., Kruse, P., Eichler, A., Muellerleile, J., Straehle, J., Jedlicka, P., Beck, J., Deller, T., Vlachos, A. Abstract: A defining feature of the brain is its ability to adapt structural and functional properties of synaptic contacts in an experience-dependent manner. In the human cortex direct experimental evidence for synaptic plasticity is currently missing. Here, we probed plasticity in human cortical slices using the vitamin A derivative all-trans retinoic acid, which has been suggested as medication for the treatment of neuropsychiatric disorders, e.g., Alzheimer's disease. Our experiments demonstrate coordinated structural and functional changes of excitatory synapses of superficial (layer 2/3) pyramidal neurons in the presence of all-trans retinoic acid. This synaptic adaptation is accompanied by ultrastructural remodeling of the calcium-storing spine apparatus organelle and requires mRNA-translation. We conclude that all-trans retinoic acid is a potent mediator of synaptic plasticity in the adult human cortex. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.26.269290v1?rss=1 Authors: Chen, H., Xie, L., Wang, Y., Zhang, H. Abstract: Metabolic energy can be used as a unified principle to control neuronal activity. However, whether and how metabolic energy alone can determine the outcome of synaptic plasticity remains unclear. In this study, a computational model of synaptic plasticity that is completely determined by energy is proposed. A simple quantitative relationship between synaptic plasticity and postsynaptic potential energy is established. Synaptic weight is directly proportional to the difference between the baseline potential energy and the suprathreshold potential energy and is constrained by the maximum energy supply. Results show that the energy constraint improves the performance of synaptic plasticity and avoids setting the hard boundary of synaptic weights. With the same set of model parameters, our model can reproduce several classical experiments in homo and heterosynaptic plasticity. The proposed model can explain the interaction mechanism of Hebbian and homeostatic plasticity at the cellular level, thereby providing a new way to deeply understand the characteristics of learning and memory. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.25.266619v1?rss=1 Authors: Devineni, A. V., Deere, J. U., Sun, B., Axel, R. Abstract: The brain creates internal representations that translate sensory stimuli into appropriate behavior. Most studies of sensory processing focus on which subsets of neurons are activated by a stimulus, but the temporal features of the neural response are also important for behavior. In the taste system, the timing of peripheral sensory responses has rarely been examined. We investigated the temporal properties of taste responses in Drosophila melanogaster and discovered that different types of taste sensory neurons show striking differences in their response dynamics. Strong responses to stimulus onset (ON responses) and offset (OFF responses) were observed in bitter-sensing neurons in the labellum, whereas bitter neurons in the leg and other classes of labellar taste neurons showed only an ON response. Individual bitter labellar neurons generate both the ON and OFF responses through a cell-intrinsic mechanism that requires canonical bitter receptors. The bitter ON and OFF responses at the periphery are propagated to dopaminergic neurons that innervate the mushroom body and mediate aversive learning. When bitter is used as a reinforcement cue, the bitter ON and OFF responses can drive opposing types of synaptic plasticity and the effect of the OFF response dominates, likely due to the rapid and preferential habituation of the ON response. Together, these studies characterize novel features of neural responses in the taste system and reveal their importance for neural circuit function. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.05.237420v1?rss=1 Authors: Popov, A., Brazhe, A., Denisov, P., Sutyagina, O., Lazareva, N., Verkhratsky, A., Semyanov, A. Abstract: Little is known about age-dependent changes in structure and function of astrocytes and of the impact of these into the cognitive decline in the senescent brain. The prevalent view on age-dependent increase in reactive astrogliosis and astrocytic hypertrophy requires scrutiny and detailed analysis. Using two-photon microscopy in conjunction with 3D reconstruction, Sholl and volume fraction analysis we demonstrate a significant reduction in the number and the length of astrocytic processes, in astrocytic territorial domains and in astrocyte-to-astrocyte coupling in the aged brain. Probing physiology of astrocytes with patch-clamp and Ca2+ imaging revealed deficits in K+ and glutamate clearance, and spatiotemporal reorganization of Ca2+ events in old astrocytes. These changes paralleled impaired synaptic long-term potentiation (LTP) in hippocampal CA1 in old mice. Our findings may explain astroglial mechanisms of age-dependent decline in learning and memory. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.04.235481v1?rss=1 Authors: Qi, C., Chen, X., Gao, X., Xu, J., Liu, S., Ge, J. Abstract: Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, psychiatric symptoms and behavioral disorders, resulting in disability and loss of self-sufficiency. Objective: To establish an AD mice model, investigate the behavioral performance, and explore the potential mechanism. Methods: Streptozotocin (STZ, 3 mg/kg) was microinjected bilaterally into the dorsal hippocampus of C57BL /6 mice to establish the AD model. Behavioral changes (anhedonia and despair, balance and motor coordination, locomotion, and learning and memory) were examined and the serum concentrations of insulin and nesfatin-1 were measured by ELISA. The activation of hippocampal microglia was assessed by immunohistochemistry and the protein expression of several molecular associated with the regulation of synaptic plasticity in the hippocampus and the prefrontal cortex (PFC) was detected via western blotting. Results: The STZ model mice showed a slower bodyweight gain and higher serum concentrations of insulin and nesfatin-1. Although there was no significant difference between groups with regard to the ability of balance and motor coordination, the model mice presented a decline of spontaneous movement and exploratory behavior, together with an impairment of learning and memory ability. Increased activated microglia was aggregated in the hippocampal dentate gyrus of model mice. Moreover, the protein expression of NMDAR2A, NMDAR2B, SynGAP, PSD95, BDNF, and p-{beta}-catenin/{beta}-catenin were remarkably decreased in the hippocampus and the PFC of model mice, and the expression of p-GSK-3{beta} (ser9)/GSK-3{beta} were reduced in the hippocampus. Conclusion: A bilateral hippocampal microinjection of STZ could successfully duplicate an AD mice model, as indicated by the impaired learning and memory and the alternated synaptic plasticity, together with the hyperactive inflammatory response in the hippocampus and the imbalanced abundance of serum insulin and nesfatin-1. Apart from these, the mechanism might be associated with the imbalanced expression of the key proteins of Wnt signaling pathway in the hippocampus and the PFC. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.03.234831v1?rss=1 Authors: Parent, M. B., Ferreira-Neto, H. C., Kruemmel, A. R., Althammer, F., Patel, A. A., Keo, S., Whitley, K. E., Cox, D. N., Stern, J. E. Abstract: Chronic heart failure (HF) is a serious disorder that afflicts more than 26 million patients worldwide. HF is comorbid with depression, anxiety and memory deficits that have serious implications for quality of life and self-care in patients who have HF. Despite evidence that cognitive performance is worse in HF patients with reduced ejection fraction than in HF patients with preserved cardiac function, there are few studies that have assessed the effects of severely reduced ejection fraction ([≤]40%) on cognition in non-human animal models. Moreover, very limited information is available regarding the effects of HF on genetic markers of synaptic plasticity in brain areas critical for memory and mood regulation. We induced HF in male rats and tested mood and anxiety (sucrose preference and elevated plus maze) and memory (spontaneous alternation and inhibitory avoidance) and measured the simultaneous expression of 84 synaptic plasticity-associated genes in dorsal (DH) and ventral hippocampus (VH), basolateral (BLA) and central amygdala (CeA,) and prefrontal cortex (PFC). We also included the hypothalamic paraventricular nucleus (PVN), which has been implicated in neurohumoral activation in HF. Our results show that rats with severely reduced ejection fraction displayed signs of polydipsia, anhedonia, increased anxiety, and impaired memory in both tasks. HF also produced a drastic downregulation of synaptic-plasticity genes in PFC and PVN, moderate decreases in DH and CeA and minimal effects in BLA and VH. Collectively, these findings identify candidate brain areas and molecular mechanisms underlying HF-induced disturbances in mood and memory. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.20.212019v1?rss=1 Authors: Puentes-Mestril, C., Delorme, J., Wang, L., Donnelly, M., Popke, D., Jiang, S., Aton, S. Abstract: Sleep and sleep loss are thought to impact synaptic plasticity, and recent studies have shown that sleep and sleep deprivation (SD) differentially affect gene transcription and protein translation in the mammalian forebrain. However, much less is known regarding how sleep and SD affect these processes in different microcircuit elements within the hippocampus and neocortex - for example, in inhibitory vs. excitatory neurons. Here we use translating ribosome affinity purification (TRAP) and in situ hybridization to characterize the effects of sleep vs. SD on abundance of ribosome-associated transcripts in Camk2a-expressing (Camk2a+) pyramidal neurons and parvalbumin-expressing (PV+) interneurons in mouse hippocampus and neocortex. We find that while both Camk2a+ neurons and PV+ interneurons in neocortex show concurrent SD-driven increases in ribosome-associated transcripts for activity-regulated effectors of plasticity and transcriptional regulation, these transcripts are minimally affected by SD in hippocampus. Similarly we find that while SD alters several ribosome-associated transcripts involved in cellular timekeeping in neocortical Camk2a+ and PV+ neurons, effects on circadian clock transcripts in hippocampus are minimal, and restricted to Camk2a+ neurons. Taken together, our results indicate that SD effects on transcripts destined for translation are both cell type- and brain region-specific, and that these effects are substantially more pronounced in the neocortex than the hippocampus. We conclude that SD-driven alterations in the strength of synapses, excitatory-inhibitory balance, and cellular timekeeping are likely more heterogeneous than previously appreciated. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.01.180372v1?rss=1 Authors: Limbacher, T., Legenstein, R. Abstract: The ability to base current computations on memories from the past is critical for many cognitive tasks such as story understanding. Hebbian-type synaptic plasticity is believed to underlie the retention of memories over medium and long time scales in the brain. However, it is unclear how such plasticity processes are integrated with computations in cortical networks. Here, we propose Hebbian Memory Networks (H-Mems), a simple neural network model that is built around a core hetero-associative network subject to Hebbian plasticity. We show that the network can be optimized to utilize the Hebbian plasticity processes for its computations. H-Mems can one-shot memorize associations between stimulus pairs and use these associations for decisions later on. Furthermore, they can solve demanding question-answering tasks on synthetic stories. Our study shows that neural network models are able to enrich their computations with memories through simple Hebbian plasticity processes. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.22.152066v1?rss=1 Authors: Galanis, C., Fellenz, M., Becker, D., Bold, C., Lichtenthaler, S. F., Mueller, U. C., Deller, T., Vlachos, A. Abstract: The physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPs in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures of APP-/- mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-{beta} (A{beta} and not by APPs, and it is neither observed in APP+/+ tissue treated with {beta}- or {gamma}-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased A{beta} levels. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.19.162172v1?rss=1 Authors: Bredenberg, C. J., Simoncelli, E. P., Savin, C. Abstract: Neural populations do not perfectly encode the sensory world: their capacity is limited by the number of neurons, metabolic and other biophysical resources, and intrinsic noise. The brain is presumably shaped by these limitations, improving efficiency by discarding some aspects of incoming sensory streams, while preferentially preserving commonly occurring, behaviorally-relevant information. Here we construct a stochastic recurrent neural circuit model that can learn efficient, task-specific sensory codes using a novel form of reward-modulated Hebbian synaptic plasticity. We illustrate the flexibility of the model by training an initially unstructured neural network to solve two different tasks: stimulus estimation, and stimulus discrimination. The network achieves high performance in both tasks by appropriately allocating resources and using its recurrent circuitry to best compensate for different levels of noise. We also show how the interaction between stimulus priors and task structure dictates the emergent network representations. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.12.147421v1?rss=1 Authors: Wang, Y., Lobb-Rabe, M., Ashley, J., Carrillo, R. A. Abstract: Throughout the nervous system, the convergence of two or more presynaptic inputs on a target cell is commonly observed. The question we ask here is to what extent converging inputs influence each other's structural and functional synaptic plasticity. In complex circuits, isolating individual inputs is difficult because postsynaptic cells can receive thousands of inputs. An ideal model to address this question is the Drosophila larval neuromuscular junction where each postsynaptic muscle cell receives inputs from two glutamatergic types of motor neurons (MNs), known as 1b and 1s MNs. Notably, each muscle is unique and receives input from a different combination of 1b and 1s motor neurons. We surveyed synapses on multiple muscles for this reason. Here, we identified a cell-specific promoter to ablate 1s MNs after innervation. Additionally, we genetically blocked 1s innervation. Then we measured 1b MN structural and functional responses using electrophysiology and microscopy. For all muscles, 1s MN ablation resulted in 1b MN synaptic expansion and increased basal neurotransmitter release. This demonstrates that 1b MNs can compensate for the loss of convergent inputs. However, only a subset of 1b MNs showed compensatory evoked activity, suggesting spontaneous and evoked plasticity are independently regulated. Finally, we used DIP- mutants that block 1s MN synaptic contacts; this eliminated robust 1b synaptic plasticity, raising the possibility that muscle co-innervation may define an activity 'set point' that is referenced when subsequent synaptic perturbations occur. This model can be tested in more complex circuits to determine if co-innervation is fundamental for input-specific plasticity. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.19.105189v1?rss=1 Authors: Park, A. J., Shetty, M. S., Baraban, J. M., Abel, T. Abstract: Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, mice lacking translin/trax exhibit some of the behavioral abnormalities found in a mouse model of fragile X syndrome. Therefore, identifying signaling pathways interacting with translin/trax to support persistent synaptic plasticity is a translationally relevant goal. Here, as a first step to achieve this goal, we have assessed the requirement of translin/trax for multiple hippocampal synaptic plasticity paradigms that rely on distinct molecular mechanisms. We found that mice lacking translin/trax exhibited selective impairment in a form of persistent hippocampal plasticity, which requires postsynaptic PKA activity. In contrast, enduring forms of plasticity that are dependent on presynaptic PKA were unaffected. Furthermore, these mice did not display exaggerated metabotropic glutamate receptor-mediated long-term synaptic depression, a hallmark of the mouse model of fragile X syndrome. Taken together, these findings demonstrate that translin/trax mediates long-term synaptic plasticity that is dependent on postsynaptic PKA signaling. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.13.093906v1?rss=1 Authors: Masoli, S., Ottaviani, A., D'Angelo, E. Abstract: The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.29.067629v1?rss=1 Authors: Jackson, J. S., Johnson, J. D., Meftah, S., Murray, T. K., Ahmed, Z., Fasiolo, M., Hutton, M. L., Isaac, J. T., O'Neill, M. J., Ashby, M. C. Abstract: Neurodegeneration driven by aberrant tau is a key feature of many dementias. Pathological stages of tauopathy are characterised by reduced synapse density and altered synapse function. Furthermore, changes in synaptic plasticity have been documented in the early stages of tauopathy suggesting that they may be a driver of later pathology. However, it remains unclear if synapse plasticity is specifically linked to the degeneration of neurons. This is partly because, in progressive dementias, pathology can vary widely from cell-to-cell along the prolonged disease time-course. To overcome this variability, we have taken a longitudinal experimental approach to track individual neurons through the progression of neurodegenerative tauopathy. Using repeated in vivo 2-photon imaging in rTg4510 transgenic mice, we have measured structural plasticity of presynaptic terminaux boutons and postsynaptic spines on individual axons and dendrites over long periods of time. By following individual neurons, we have measured synapse density across the neuronal population and tracked changes in synapse turnover in each neuron. We found that tauopathy drives a reduction in density of both presynaptic and postsynaptic structures and that this is partially driven by degeneration of individual axons and dendrites that are spread widely across the disease time-course. Both synaptic loss and neuronal degeneration was ameliorated by reduction in expression of the aberrant P301L transgene, but only if that reduction was initiated early in disease progression. Notably, neurite degeneration was preceded by alterations in synapse turnover that contrasted in axons and dendrites. In dendrites destined to die, there was a dramatic loss of spines in the week immediately before degeneration. In contrast, axonal degeneration was preceded by a progressive attenuation of presynaptic turnover that started many weeks before axon disappearance. Therefore, changes in synapse plasticity are harbingers of degeneration of individual neurites that occur at differing stages of tau-driven neurodegenerative disease, suggesting a cell or neurite autonomous process. Furthermore, the links between synapse plasticity and degeneration are distinct in axonal and dendritic compartments. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.28.066696v1?rss=1 Authors: Aponte-Santiago, N. A., Ormerod, K. G., Akbergenova, Y., Littleton, J. T. Abstract: Structural and functional plasticity induced by neuronal competition is a common feature of developing nervous systems. However, the rules governing how postsynaptic cells differentiate between presynaptic inputs are unclear. In this study we characterized synaptic interactions following manipulations of Ib tonic or Is phasic glutamatergic motoneurons that co-innervate postsynaptic muscles at Drosophila neuromuscular junctions (NMJs). After identifying drivers for each neuronal subtype, we performed ablation or genetic manipulations to alter neuronal activity and examined the effects on synaptic innervation and function. Ablation of either Ib or Is resulted in decreased muscle response, with some functional compensation occurring in the tonic Ib input when Is was missing. In contrast, the phasic Is terminal failed to show functional or structural changes following loss of the co-innervating Ib input. Decreasing the activity of the Ib or Is neuron with tetanus toxin light chain resulted in structural changes in muscle innervation. Decreased Ib activity resulted in reduced active zone (AZ) number and decreased postsynaptic subsynaptic reticulum (SSR) volume, with the emergence of filopodial-like protrusions from synaptic boutons of the Ib input. Decreased Is activity did not induce structural changes at its own synapses, but the co-innervating Ib motoneuron increased the number of synaptic boutons and AZs it formed. These findings indicate tonic and phasic neurons respond independently to changes in activity, with either functional or structural alterations in the tonic motoneuron occurring following ablation or reduced activity of the co-innervating phasic input, respectively. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.27.064725v1?rss=1 Authors: Rasiah, N., Rosenegger, D., Daviu Abant, N., Fuzesi, T., Muir, J., Sterley, T. L., Bains, J. S. Abstract: An increase in circulating glucocorticoids (CORT) is an essential part of the response to stress. Sustained elevations of CORT, however, have dramatic consequences on behavior, endocrine systems and peripheral organs. Critically, they dampen the endocrine response to acute challenges and decrease intrinsic excitability of corticotropin-releasing hormone neurons in the paraventricular nucleus (CRHPVN), suggesting key circuits may be less responsive to stress. Here, we make the surprising discovery that CRHPVN neurons harness a form of adaptive synaptic scaling to escape the persistent negative feedback pressure from CORT and maintain stable output in vivo. Specifically, there is an increase in glutamatergic drive to these cells that is mediated by a postsynaptic, multiplicative increase in synaptic strength. These findings suggest that dysfunctions associated with chronic stress may not be due to the primary actions of CORT, but instead reflect the emergence of synaptic adaptations as networks seek to re-establish intrinsic activity setpoints. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.26.061515v1?rss=1 Authors: Akil, A. E., Rosenbaum, R., Josic, K. Abstract: The dynamics of local cortical networks are irregular, but correlated. Dynamic excitatory-inhibitory balance is a plausible mechanism that generates such irregular activity, but it remains unclear how balance is achieved and maintained in plastic neural networks. In particular, it is not fully understood how plasticity induced changes in the network affect balance, and in turn, how correlated, balanced activity impacts learning. How does the dynamics of balanced networks change under different plasticity rules? How does correlated spiking activity in recurrent networks change the evolution of weights, their eventual magnitude, and structure across the network? To address these questions, we develop a general theory of plasticity in balanced networks. We show that balance can be attained and maintained under plasticity induced weight changes. We find that correlations in the input mildly, but significantly affect the evolution of synaptic weights. Under certain plasticity rules, we find an emergence of correlations between firing rates and synaptic weights. Under these rules, synaptic weights converge to a stable manifold in weight space with their final configuration dependent on the initial state of the network. Lastly, we show that our framework can also describe the dynamics of plastic balanced networks when subsets of neurons receive targeted optogenetic input. Copy rights belong to original authors. Visit the link for more info
Cells that fire together wire together. Hebbian mechanisms of plasticity, summarized by that simple phrase, have dominated the field of learning and memory for decades. However, they present limitations when applied to many behavioral paradigms. On this episode Jeremy, Audrey, and Andre sit down with Dr. Jeff Magee, Howard Hughes Medical Institute Investigator, The Cullen Foundation Distinguished Endowed Chair at the Jan and Dan Duncan Neurological Research Institute, and Professor in the Department of Neuroscience at Baylor College of Medicine. They'll discuss how Dr. Magee's work looking at dendritic processes led him and his group to discover a new plasticity paradigm, in place field learning that breaks from traditional Hebbian rules. Hear also how Dr. Magee keeps active in the lab and his advice for young investigators.
As endurance athletes, we know that recovery is key in optimizing performance. We also deal with pain on a regular basis. For those reasons, many of us are curious about the medicinal benefits of cannabis as an anti-inflammatory and pain remediator. But with all the hype out there, how do you know what products to choose? Do you need CBD, THC or both? How do you identify a quality supplier? Don Moxley is a respected exercise physiologist who specializes in tracking and improving performance and alleviating unnecessary suffering. His work with elite athletes led to an interest in the role of cannabinoids in the central nervous system and his current role as an advisor at Mendi, a company using cannabis to build recovery tools that optimize performance. Don has 30-plus years of classroom and industry leadership to his credit, and as an athlete, he served as captain of The Ohio State University Wrestling Team, earning a Big 10 Title in 1985. Today, Don joins us to discuss the medicinal value of cannabis and explain the differences among THC, CBD, THCA and CBDA. He describes the role of CBD in athlete recovery, sharing how he manages his own knee pain and inflammation with cannabis. Don also uncovers the important role of anandamides in the central nervous system and addresses how elite athletes can leverage intentional recovery. Listen in for insight on the appropriate ratios of THC and CBD in topical and ingested products and learn to be an informed consumer of cannabis! Topics Covered [2:32] The different species of cannabis plants Vary by percentage of TCHA + CBDA Neither psychoactive until heated [5:16] The medicinal value of cannabis Powerful anti-inflammatory Pain remediation [7:44] The role of CBD + THC in athlete recovery CBD + CBDA seems to give bump in HRV Find right combo of THCA, THC, CDBA + CBD [11:38] Don’s personal experience with cannabis Manages knee pain and inflammation with CBD Topical + oral ingestion relieves pain, anxiety [14:18] Don’s advice on being an informed consumer Pay less than $50/gram of CBD Ask for certificate of analysis (COA) [17:46] The THC + CBD ratios Don recommends 1:1 THC to CBD for topical, 250 mg of each in 2 oz. jar Ingest 1 mg of CBD/lb. body weight daily (pain, anxiety) [19:11] How cannabis plants have evolved over time From 5% to 28% THC by weight since 1970’s Starting to breed for CBD content now Need both THC + CBD for relaxing effect [21:58] The impact of smoking before a race May help regulate pain Not recommended [25:32] The role of anandamides in the nervous system Exercise benefits by building anandamides Fear conditioning leads to drop (causes hypervigilance) Consumption of exogenous cannabinoids to normalize [30:49] Don’s insight around intentional recovery Elite athletes must alleviate environmental stressors Chronic cannabinoid deficiency limits performance [33:58] Don’s advice around finding cannabis products Start with quality CBD product, CBDA if available Look in established markets (WA, OR, CO + CA) [36:15] Don’s tips for Ali Fitness listeners Shed tradition to see new opportunities Use HRV as tool to monitor benefit and recovery Learn More About Don Moxley Mendi Don on LinkedIn Don on Twitter Don on Facebook Don on Instagram Resources ‘Microdeletion in a FAAH Pseudogene Identified in a Patient with High Anandamide Concentrations and Pain Insensitivity’ in The British Journal of Anaesthesia ‘Fear Conditioning, Synaptic Plasticity and the Amygdala: Implications for Posttraumatic Stress Disorder’ in Neuropsychiatric Disorders Dr. Ron Gharbo Dr. Ethan Russo Elite HRV Oura Ring Polar Heart Rate Transmitters on Amazon
On this episode of Max Planck Florida's Neurotransmissions Dr. Paul Evans, former Postdoc in the Yasuda lab and current MPFI Academic Programs Coordinator, and Dr. Audrey Bonnan, Postdoc in the Christie lab, are joined by Dr. Claudia Bagni. Dr. Bagni is the Professor and Chair in Fundamental Neuroscience at the University of Lausanne where her group has been studying the cellular and molecular mechanisms of synaptic plasticity and their dysfunction in inherited intellectual disabilities. Learn about how Dr. Bagni's research has led her beyond neuroscience into cancer research and how she has pursued opportunities to translate her research from the bench to the clinic. Enjoy!
HVMN Podcast: Evidence-based Nutrition, Fitness, & Biohacking
Welcome to the first episode of our brand-new monthly series: Research Round-up. To stay up to date on the cutting-edge of health and performance, our HVMN Research Lead Dr. Brianna Stubbs tends to read a lot of scientific literature...A LOT. In fact, she wants to share all this stored up knowledge with you: Our podcast listeners. Every month, she will dive into the latest, most relevant, and exciting research papers. It's tough to get through a written study, and that's why Dr. Stubbs is here to walk us through the experiment process, dissect the results and implications, and candidly share her own thoughts on the paper and subject as a whole. This month, Dr. Stubbs dives into three papers, all relating to the topic of aging and longevity: BHB Prevents Vascular Senescence Through hnRNP A1-Mediated Upregulation of Oct4 Quantitative Analysis of NAD Synthesis-Breakdown Fluxes Young Blood Reverses Age-Related Impairments in Cognitive Function and Synaptic Plasticity in Mice ------------------------------------------------------------------------------ Visit our website to learn more: https://go.hvmn.com/podcast-audio Take a short survey that will help us improve the podcast and be entered in a HVMN Ketone giveaway: https://go.hvmn.com/podcastsurvey We also want to hear from our listeners/viewers! Contact podcast@hvmn.com with any feedback, questions, and guest suggestions! Write a review for us on iTunes, let us know via email, and we'll send you a one-month's supply of Kado (https://go.hvmn.com/kado-podcast).
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Dr. David Diamond is a University of South Florida professor in the departments of psychology, molecular pharmacology and physiology and director of the USF Neuroscience Collaborative. He is well known for research that looks at the effects of stress on brain, memory and synaptic plasticity. A primary research project over the past few decades has been the study of treatments for combat veterans and civilians with PTSD. Although his academic specialty is neuroscience, recently he has been closely examining the role of fat and cholesterol in heart disease. He began looking into lipids after test results showed his triglycerides were through the roof. He also launched a critical look into the effectiveness of statins, a class of drugs doctors frequently prescribe to help people lower cholesterol levels in their blood. Dr. Diamond’s findings contradicted the low-fat, high-carb diet that he, as well as many Americans, had been advised to follow. This led him to explore ways for people to optimize their diet for cardiovascular health. He eventually created a graduate and undergraduate seminar entitled, “Myths and Deception in Medical Research.” A lecture he gave at the university entitled “How Bad Science and Big Business Created the Obesity Epidemic” is now a YouTube video with nearly 200,000 views. The lecture focused on how “flawed and deceptive science demonized saturated fats and created the myth that a low-fat, plant-based diet is good for your health.” Dr. Diamond received his B.S. in biology from the University of California, Irvine in the 1980. He continued his post-graduate work at the university and earned a Ph.D. in biology with a specialization in behavioral neuroscience. From 1986 to 1997, Dr. Diamond was an assistant professor in the Department of Pharmacology in the University of Colorado Health Sciences Center in Denver. He then moved to University of South Florida and since 2003 has been a professor in the departments of psychology, molecular pharmacology and physiology. In addition to directing USF’s Neuroscience Collaborative, Dr. Diamond also is the director of the university’s Center for Preclinical and Clinical Research on Post-Traumatic Stress Disorder. His research projects at the university have ranged from “The Effects of Stress on Brain, Memory and Synaptic Plasticity” to “The Cognitive and Neurobiological Perspectives on Why Parents Lose Awareness of Children in Cars.” Dr. Diamond has served on federal government study sections and committees evaluating research on the neurobiology of stress and memory and has more than 100 publications, reviews, and book chapters on the brain and memory. He is a fellow in the American Institute of Stress and in 2015 he received the award for Outstanding Contribution to Science from the Riga Diabetes and Obesity World Congress. In 2015, Diamond also received the University of South Florida International Travel Award. Links: USF lecture: “How Bad Science and Big Business Created the Obesity Epidemic” https://www.youtube.com/watch?v=3vr-c8GeT34 IHMC lecture: “An Update on Demonization and Deception in Research of Saturday Fat, Cholesterol and Heart Disease --http://www.ihmc.us/lectures/20170531/ Show notes: 4:31: Ken and Dawn welcome David to the show. 4:42: Dawn comments on how David has always been interested in science and even wanted to be a physician as a child. She also asks him about majoring in biology and receiving his PhD from the University of California, Irvine. 5:41: Dawn asks David about his varied research topics at the University of South Florida, including cognitive and neurobiological perspectives on why parents lose awareness of children in cars. 7:00: Ken asks David what led him to research cardiovascular disease and statins, since he has such an extensive background in memory and PTSD research. 7:46: Dawn mentions David’s lecture he gave at the University South Florida entitled,
David Sweatt and John Halblitz explain how DNA methylation controls glutamatergic synaptic scaling, a type of synaptic plasticity important for learning and memory.
Catherine Wasser and Joachim Herz have found that normal synaptic function and fear learning require glycosylation of the apolipoprotein E receptor Apoer2.
Background: Neurofibromatosis type 1 (NF1) is one of the most common genetic disorders causing learning disabilities by mutations in the neurofibromin gene, an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of function mutation of the neurofibromin gene resulted in increased gamma aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic plasticity and deficits in attentional performance. Most importantly, these defictis were normalized by lovastatin. This placebo-controlled, double blind, randomized study aimed to investigate synaptic plasticity and cognition in humans with NF1 and tried to answer the question whether potential deficits may be rescued by lovastatin. Methods: In NF1 patients (n = 11; 19-44 years) and healthy controls (HC; n = 11; 19-31 years) paired pulse transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (paired pulse) and synaptic plasticity (paired associative stimulation). On behavioural level the Test of Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin for 4 days on all these parameters, a placebo-controlled, double blind, randomized trial was performed. Results: In patients with NF1, lovastatin revealed significant decrease of intracortical inhibition, significant increase of synaptic plasticity as well as significant increase of phasic alertness. Compared to HC, patients with NF1 exposed increased intracortical inhibition, impaired synaptic plasticity and deficits in phasic alertness. Conclusions: This study demonstrates, for the first time, a link between a pathological RAS pathway activity, intracortical inhibition and impaired synaptic plasticity and its rescue by lovastatin in humans. Our findings revealed mechanisms of attention disorders in humans with NF1 and support the idea of a potential clinical benefit of lovastatin as a therapeutic option.
The neurotrophic factor BDNF has opposite effects on cocaine- and morphine-induced neuroplasticity.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Fri, 8 Oct 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/13030/ https://edoc.ub.uni-muenchen.de/13030/1/Krupp_Alexander.pdf Krupp, Alexander ddc:570, ddc:500, Fakultät für Biologie
Vortrag im Seminar des TR 3
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Thu, 16 Jul 2009 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/10391/ https://edoc.ub.uni-muenchen.de/10391/1/Essmann_Clara.pdf Essmann, Clara Luise ddc:570, ddc:500, Fakultät für Biologie
Enhanced Audio PodcastAired date: 3/31/2008 12:00:00 PM Eastern Time
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Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 02/06
The present work focused on the role of the cannabinoid receptor type 1 (CB1) in synaptic plasticity, memory and emotionality in mice. CB1 is abundantly expressed in the central nervous system and is mainly (if not exclusively) located on GABAergic and glutamatergic nerve cells. CB1 is a G-protein coupled receptor which is essentially inhibiting transmitter release from presynaptic GABAergic or glutamatergic nerve terminals. To differentiate between the physiological significance of CB1 expressed on glutamatergic and GABAergic nerve terminals, the studies included work with three different CB1-deficient mouse lines: A conventional knock-out mouse line (total-CB1- ko mice) with a deficiency of CB1 in the entire brain and two conditional knock-out mouse lines using the Cre/lox P recombination system, and leading to cell type specific deficiency of CB1 on GABAergic neurons (GABA-CB1-ko mice) or glutamatergic neurons (Glu-CB1-ko mice). As a common model for alterations in synaptic plasticity and hippocampus-dependent memory, we studied long-term potentiation in the hippocampus at first. The hippocampus is an essential brain structure being involved in spatial and episodic-like memory. We showed that there is an increase of hippocampal LTP in vivo at the perforant path-dentate gyrus granule cell synapse in total-CB1-ko mice, but failed to detect any difference in LTP levels for GABA-CB1-ko and Glu-CB1-ko mice. Also, short-term plasticity using a paired-pulse stimulation protocol is unchanged in the three mouse lines. Eventually, augmented theta rhythm that is believed to underlie enhanced cognitive abilities could not be found in total-CB1-ko mice. Our hypothesis of memory improvement in CB1-deficient mouse lines could not be verified in three tests for memory that are based on a spontaneous preference for novelty: The social recognition test, the object recognition test and the open field habituation test. We consequently tested the mice in two memory tasks that rely on an aversive test situation. In the water maze spatial discrimination task, again no differences could be assessed for acquisition of the task in total-CB1-ko and Glu-CB1-ko mice. Curiously, Glu-CB1-ko mice demonstrate more flexible behaviour in reversal learning indicating that CB1 on glutamatergic neurons may lead to perseverant and persistent behaviour. Eventually, we could show for the first time that there is a differential contribution of CB1 on either GABAergic neurons or glutamatergic neurons in the background contextual fear conditioning task. Here, mice were tested in the shock context and in a different context containing the grid floor as a similar aspect to the shock context, called grid context. GABA-CB1-ko mice reveal increased fearful behaviour specifically in the grid context. This might indicate an increased context generalisation and/or a feature learning strategy in GABA-CB1-ko mice. In contrast, Glu-CB1-ko mice display increased fearful behaviour specifically for the shock context, indicating a conjunctive learning strategy. Total-CB1-ko mice showed an increased fear response in both contexts, representing a mixed phenotype of Glu-CB1-ko and GABA-CB1-ko mice. Another novel finding confirming a large body of evidence is the fact that total-CB1-ko and Glu-CB1-ko mice manifest a deficit of extinction for the conditioned tone, providing first evidence that CB1 on glutamatergic neurons is essential for short-term extinction of auditory-cued fear memory. Any changes in memory performance might be obscured by altered emotionality in the knockout mouse lines. In classical tests for anxiety such as the elevated plusmaze and the light/dark box, we found a tendency of increased anxiety in total-CB1- ko and Glu-CB1-ko mice and a tendency of a decrease of anxiety in GABA-CB1-komice at most. Strikingly, we were able to show that CB1-ko and Glu-CB1-ko mice, in contrast to GABA-CB1-ko, avoid the open arms of the elevated plus-maze more than wildtype mice on a second exposure to the maze indicating an increased one-trial sensitisation. Furthermore remarkably, CB1-ko and Glu-CB1-ko mice showed increased anxiety-related behaviour whereas GABA-CB1-ko mice revealed an unchanged or anxiolytic phenotype in three different tests of emotionality: The open field test, the novel object exploration test and the novel juvenile exploration test. These tests were carried out under low and high light conditions. Here, as opposed to the elevated plus-maze and the light/dark box, the animals cannot retract from an aversive situation that is bright light in the testing environment which may cause sufficient activation of the endocannabinoid system thus leading to a detectable and profound phenotype in the animals. Interestingly, altered emotionality seems to depend on the averseness of the test situation, as CB1-ko and Glu-CB1-ko animals do not or only mildly differ from their wildtype littermates under lowly aversive conditions but show increased anxiety under highly aversive conditions in the aforementioned tests. This strongly suggests that the endocannabinoid system might dampen states of anxiety in highly aversive and stressful environments. More precisely, CB1 on GABAergic neurons rather leads to an anxiogenic effect, whereas CB1 on glutamatergic neurons prominently leads to an anxiolytic phenotype which we refer to as “the Yin and the Yang effect” of CB1 in emotionality. Altogether, our study illustrates the value of conditional mouse mutants for which celltype specific ablation of a gene of interest exist in order to understand the role of CB1 in synaptic plasticity, memory and emotionality. Our findings add another level of complexity to the picture of endocannabinoid action in fear and anxiety, which has to be considered if the endocannabinoid system is going to be exploited as a therapeutic target for the treatment of anxiety disorders.
Enhanced Audio PodcastAired date: 4/9/2007 12:00:00 PM Eastern Time
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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.19.048819v1?rss=1 Authors: Prieto, M., Folci, A., Poupon, G., Schiavi, S., Buzzelli, V., Francois, U., Pousinha, P., Lattuada, N., Abelanet, S., Pronot, M., Castagnola, S., Chafai, M., Khayachi, A., Brau, F., Deval, E., Francolini, M., Bardoni, B., Humeau, Y., Trezza, V., Martin, S. Abstract: Copy rights belong to original authors. Visit the link for more info
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