Forward-most portion of the brainstem
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Why doesn't the MESENCEPHALON further subdivide into larger regions of the brain?In this episode, we will expand on the neurulation time and focus on the brain formation, spotlighting the proencephalon, mesencephalon, and rhombencephalon, which emerge around days 22–23 of embryonic life. The proencephalon (forebrain) splits into the telencephalon—think cerebral hemispheres for cognition—and the diencephalon, home to the thalamus and hypothalamus for sensory and hormonal control. Meanwhile, the rhombencephalon (hindbrain) divides into the metencephalon (pons and cerebellum, key for movement) and myelencephalon (medulla, handling [mostly] autonomic essentials like breathing). The mesencephalon stands out as a non-subdividing relay hub. The mesencephalon offers tremendous insights into the Autistic phenotype with its roles in biasing the living organism's attention to the environment.Autism and the Womb https://youtu.be/NOVp4mIrougAutism, Neurulation, & Embryogenesis https://youtu.be/TXkc93uGNuwAutism & Eye Movements https://youtu.be/1amB5e9qzg4Autism & Sensory Processing Part 1 https://youtu.be/HPvwvtu5hB4Autism & Sensory Processing Part 2 https://youtu.be/iWy9RligzicDaylight Computer Company https://daylightcomputer.comuse "autism" in the discount code for $25 coupon.This is the future of tech.Chroma Light Therapy https://getchroma.couse "autism" for a 10% discount,0:00 Daylight Computer Company04:22 Neuralation and Brain Development05:09 Maternal Factors and Biomarkers (Tyrosine, Hypothyroidism, etc.)06:46 Tryptophan and Its Role in Embryogenesis08:34 Environmental Insults and Toxins09:19 Embryogenesis and Brain Formation (Proencephalon, Mesencephalon, Rhombencephalon10:43 Telencephalon10:57 Diencephalon12:34 Rhombencephalon12:52 Metencephalon13:35 Myelencephalon15:12 Evolutionary Perspective of the Mesencephalon21:39 Chroma Light Devices24:48 Mesencephalon's Role in Motor Control, Sensory Processing, and Autism; 27:12 Extrapyramidal motor system; Substantia Nigra, Red Nucleus30:11 Additional Nuclei of the Midbrain; Ocular Motor Nuclei; Edingher-Westphal; Trochlear nerve 31:58 Paraaqueductal Gray (PAG), "Retard Strength" and Its Role in Pain, Behaviors and Autism; "Freezing" in Flight, Fight, & Freeze 36:00 Eye Movements; learning & Neuroplasticity; Motor Planning, Proprioception, Language and Speech 38:20 Wrap UpX: https://x.com/rps47586Hopp: https://www.hopp.bio/fromthespectrumYT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuAemail: info.fromthespectrum@gmail.com
In this episode, we discuss the connections between autism and eye movements, starting with the underappreciated role of eyes in human biology. We emphasize the significance of the retina, which is central to both image-forming and non-image-forming functions of vision. The discussion takes a turn towards how blind individuals also leverage their eyes for biological functions beyond sight, highlighting the pervasive influence of visual systems on human physiology. We explore the superior colliculus, an essential brain region that integrates sensory information from various sources, including vision, to direct our attention and reflexive responses. This area is crucial in understanding how sensory input differently, particularly in terms of attention bias and threat detection, which could explain some of the unique sensory experiences in Autism.We then touch upon the dorsal anterior cingulate cortex (dACC) and the roles in error detection, conflict monitoring, and effort evaluation. The dACC's involvement in these cognitive processes can provide insights into why certain social cues or environmental stimuli might be overwhelming or less salient for individuals on the spectrum. Additionally, the episode covers oxytocin, a hormone/neuropeptide involved in social bonding and emotional regulation, discussing its synthesis through magnocellular and parvocellular pathways in vision. What do you think oxytocin is doing here, for the cub and for you? https://www.reddit.com/r/NatureIsFuckingLit/comments/11q03yn/a_cub_puma_admiring_his_mother/?rdt=64743Eye-Tracking as an Early Biomarker of Autism https://youtu.be/fJpIRHOZZO4The Roles of Oxytocin and Vasopressin in the Autistic phenotype https://youtu.be/DAtmC-s1_e0Mesencephalon https://en.wikipedia.org/wiki/Midbrain#:~:text=The%20midbrain%20or%20mesencephalon%20is,view%20of%20one%20cerebellar%20hemisphere.00:00 - Introduction to Autism and Eye Movements; importance of eyes in biology, specifically mentioning the retina as a key player.04:19 - Non-Image Functions and Master Clock; Melanopsin; SCN- master clock08:13 - Eye Tracking and Autism Diagnosis; effectiveness at 14 months of age12:23 - Biological Underpinnings of Eye Movements in Autism; dorsal anterior cingulate cortex (dACC), Superior Colliculus & Mesencephalon & sensory integration, attention in the context of Autism & brain development16:48 - Sensory Integration & Superior Colliculus and Reflexive Responses & Biasing Attention.20:58 - Developmental Aspects of Autism; embryonic stage before the central nervous system25:11 - Vision and Autonomic Nervous Systemvision and breathing can influence stress and calmness & bidirectional connections27:47 Reviews/Ratings and Contact InformationX: https://x.com/rps47586Hopp: https://www.hopp.bio/fromthespectrumYT: https://www.youtube.com/channel/UCGxEzLKXkjppo3nqmpXpzuAemail: info.fromthespectrum@gmail.com
We have been looking at different aspects of communication here at the Edges of Lean, and one aspect I wanted to explore more was the neuroscience of communication. Creative entrepreneur, writer, and coach Aurora Winter joins me to bring insight on that topic and highlight the power of stories. Aurora Winter Aurora Winter is a successful entrepreneur, bestselling author, TV writer-producer, and founder of SamePagePublishing.com. With expertise in film and neuroscience, Aurora helps people craft impactful stories that boost brands, books, and businesses. Winner of the Outstanding Nonfiction Book of the Year Award, her book "Turn Words Into Wealth" reveals seven ways to generate seven figures. She emphasizes the power of words to elevate income, impact, and influence. Passionate about meaningful discussions and valuable content creation, Aurora covers various topics, including the neuroscience of communication, marketing, pivoting, creating multiple income streams, turning books into movies, writing fiction and nonfiction, publishing, and more. KEY TOPICS IN THIS PODCAST: 00:00:14 - Exploring the Neuroscience of Communication 00:00:58 - Aurora Winter's Background and Journey 00:08:34 - Addressing the Midbrain in Communication 00:14:34 - The Power of Stories in Communication 00:20:40 - Impact of Stories on Belonging and Meaning 00:27:13 - Stories as Tools for Change and Inspiration 00:36:51 - Where to Find Aurora Winter Online 00:41:54 - Advice for Young People Starting Out KEY TAKEAWAYS: Communication is a powerful tool that can significantly impact productivity and profitability. The midbrain, which is responsible for social connection and belonging, should also be addressed by highlighting the value of the message to others. Stories are a powerful tool in communication as they convey values and provide meaning to the audience. Opening a presentation with a question or half of a story can create interest and engagement from the audience. Fiction, particularly science fiction, can shape and change the world by introducing new ideas and perspectives. When starting any endeavor, it is vital to follow your interests and passions, explore different opportunities, and always look for beauty in every situation. Memorable Quotes From Aurora Winter "Stories teach values, and science provides information." CONNECT WITH Aurora Winter LinkedIn: https://www.linkedin.com/in/aurorawinter/ Website: https://www.aurorawinter.com/ Gifts: 1. www.turnwordsintowealth.com 2. www.magicmysteryandthemultiverse.com
The exact origin of awareness and consciousness in the brain is a complex and debated topic in neuroscience and philosophy. Consciousness involves a range of cognitive functions, self-awareness, perception, and subjective experiences, and it doesn't have a single, localized “start” in the brain. Instead, it arises from the intricate interactions of various brain regions. However, some brain regions and networks are commonly associated with aspects of consciousness: 1. Thalamus: Often referred to as the “gateway to the cortex,” the thalamus plays a crucial role in relaying sensory information to different regions of the brain, contributing to our perception of the external world. 2. Cortex: The outer layer of the brain, particularly the prefrontal cortex, is involved in higher cognitive functions, decision-making, and self-awareness. 3. Midbrain and Brainstem: The midbrain and brainstem regulate basic functions such as arousal, attention, and autonomic responses. These are fundamental for maintaining a state of consciousness. 4. Global Workspace Theory: This theory suggests that consciousness arises from the global availability of information in the brain, allowing different specialized regions to communicate and integrate information. 5. Default Mode Network (DMN): The DMN is a network of brain regions that is active when an individual is not focused on the outside world, but rather engaged in internal thoughts. It's associated with self-awareness and mind-wandering. --- Send in a voice message: https://podcasters.spotify.com/pod/show/destoday/message
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.25.550491v1?rss=1 Authors: Gartside, S. E., Rees, A., Olthof, B. M. Abstract: We have recently reported that the central nucleus of the inferior colliculus (the auditory midbrain) is innervated by glutamatergic pyramidal cells originating not only in auditory cortex (AC) but also in multiple, non-auditory, regions of the cerebral cortex. Using optogenetics and electrical stimulation, we investigated the functional properties of these descending connections in vivo in anaesthetised rats. A retrograde virus encoding green fluorescent protein (GFP) and channelrhodopsin (ChR2) injected into the central nucleus of the inferior colliculus (ICC), labelled discrete groups of cells in multiple areas of the cerebral cortex. Light stimulation of AC and M1 caused local activation of cortical neurones and increased the firing rate of neurones in ICc indicating a direct excitatory input from AC and M1 to ICC. Electrical stimulation of M1, secondary motor, somatosensory and prefrontal cortical regions evoked short, fixed latency firing events in ICC as well as longer latency, longer duration increases in firing activity. The short latency events were singular spikes of consistent shape and size likely resulting from monosynaptic excitation of individual ICC units. The longer latency responses comprised multiple units and spikes occurred with significant temporal jitter suggesting polysynaptic activation of local circuits within the ICC. The probability of the monosynaptic event, the magnitude of the polysynaptic response, and the area of ICC affected were dependent on the stimulus current. Our data are consistent with cortical regions exerting an important excitatory direct and indirect regulation of ICc neurones. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In this episode, I talk to Gordon Brewer. He talks about how he decided to become a therapist, his upbringing, his family, as well as his highly successful PsychCraft Network, which I joined a few weeks ago. Gordon also talks about neurology and how it relates to the brain. I truly enjoyed our conversation on spirituality, starting a business of any kind and how difficult and fulfilling (yes both) it can be. Gordon is the voice behind the Practice of Therapy Podcast and blog which provides resources for clinicians in private practice. He is also group practice owner in Kingsport, TN. He is a licensed marital and family therapist with 20 plus years experience in the field. Gordon loves helping people find meaning and purpose in their lives and relationships. He is also the founder of the PsychCraft Network of podcasts and has another podcast called the Kindness and Compassion Podcast. The PsychCraft Network can be found here.His website can be found here.His other podcast, Kindness and Compassion, can be found here.YouTube Channel For The PodcastCoaching Program
The Midbrain is the topmost part of the Brainstem, located between the Forebrain and the Hindbrain, and serves as a role in integrating the brain and the Spinal Cord, just like the Pons and Medulla. The Midbrain itself is made of three main formations, the Colliculi, the Tegmentum, and the Cerebral Peduncles, and is directly connected to the Oculomotor and Trochlear Cranial Nerves, controlling eye and eyelid movement. In this fast-facts episode, Edward reviews the Midbrain's form and function, as well as the key features that make us who we are.To create this episode, I used information provided by the University of Queensland's Queensland Brain Institute which can be found here: https://qbi.uq.edu.au/brain/brain-anatomy/midbrainNo statement, phrase, or episode of this series—or any episode in this podcast—are intended to treat, diagnose, cure, prevent, or otherwise change your mind or body in any form or manner. This podcast—and this series especially—is meant purely for education purposes for the common person. Please do not rely on any of the information I share in this podcast in any way for your medical or psychological treatment. If you feel that you may have a condition mentioned or not mentioned in this podcast, do not come to me. Instead, immediately go to a trusted psychiatrist, psychologist, therapist, counselor, or other reliable source of information and help for further guidance. Never disregard professional, psychological, or medical advice—nor delay in the seeking of this advice—because of something that you have heard or read from this podcast, this podcast's episode descriptions, this podcast's promotional materials, or any other information explicitly or implicitly generated from this podcast.-----If you love this podcast, show your support by rating, subscribing, and downloading! The best way to support me is by sharing this podcast with others—the more people can learn, the better we can understand the crazy world we live in :DI realize that this episode is coming back after a very long hiatus--I have had a few issues with my podcast server, but the rest of the episodes of this season will be published in the next few days :) Sorry for the delays and thank you for your patience!
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.20.533485v1?rss=1 Authors: Jarazo, J., Santos da Silva, E., Glaab, E., Perez-Bercoff, D., Schwamborn, J. C. Abstract: COVID-19 is mainly associated with respiratory symptoms, although several reports showed that SARS-CoV-2 affects the nervous system. We evaluated the effects of infection in prolonged culture of midbrain organoids, showing that the virus induces changes in gene expression, and fragmentation and loss of dopaminergic neurons. Our findings highlight the direct viral-induced damage to midbrain organoids indicating the relevance of assessing the neurological long-term evolution of COVID-19 patients. 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/2023.03.02.530856v1?rss=1 Authors: Hoang, I. B., Munier, J. J., Verghese, A., Greer, Z., Millard, S. J., DiFazio, L. E., Sercander, C., Izquierdo, A., Sharpe, M. J. Abstract: Behavior is often dichotomized into model-free and model-based systems. Model-free behavior prioritizes associations that have high value, regardless of the specific consequence or circumstance. In contrast, model-based behavior involves considering all possible outcomes to produce behavior that best fits the current circumstance. We typically exhibit a mixture of these behaviors so we can trade-off efficiency and flexibility. However, substance use disorder shifts behavior more strongly towards model-free systems, which produces a difficulty abstaining from drug-seeking due to an inability to withhold making the model-free high-value response 3-10. The lateral hypothalamus (LH) is implicated in substance use disorder and we have demonstrated that this region is critical to Pavlovian cue-reward learning. However, it is unknown whether learning occurring in LH is model-free or model-based, where the necessary teaching signal comes from to facilitate learning in LH, and whether this is relevant for learning deficits that drive substance use disorder. Here, we reveal that learning occurring in the LH is model-based. Further, we confirm the existence of an understudied projection extending from dopamine neurons in the ventral tegmental area (VTA) to the LH and demonstrate that this input underlies model-based learning in LH. Finally, we examine the impact of methamphetamine self-administration on LH-dependent model-based processes. These experiments reveal that a history of methamphetamine administration enhances the model-based control that Pavlovian cues have over decision-making, which was accompanied by a bidirectional strengthening of the LH to VTA circuit. Together, this work reveals a novel bidirectional circuit that underlies model-based learning and is relevant to the behavioral and cognitive changes that arise with substance use disorders. This circuit represents a new addition to models of addiction, which focus on instrumental components of drug addiction and increases in model-free habits after drug exposure. 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/2023.02.10.527867v1?rss=1 Authors: Corenblum, M. J., McRobbie-Johnson, A., Carruth, E., Bernard, K., Luo, M., Mandarino, L. J., Peterson, S., Billheimer, D., Maley, T., Eggers, E. D., Madhavan, L. Abstract: Understanding the mechanisms causing Parkinsons disease (PD) is vital to the development of much needed early diagnostics and therapeutics for this debilitating condition. Here, we report cellular and molecular alterations in skin fibroblasts of late-onset sporadic PD subjects, that were recapitulated in matched induced pluripotent stem cell (iPSC)-derived midbrain dopamine (DA) neurons, reprogrammed from the same fibroblasts. Specific changes in growth, morphology, reactive oxygen species levels, mitochondrial function, and autophagy, were seen in both the PD fibroblasts and DA neurons, as compared to their respective controls. Additionally, significant alterations in alpha synuclein expression and electrical activity were also noted in the PD DA neurons. Interestingly, although the fibroblast and neuronal phenotypes were similar to each other, they also differed in their nature and scale. Furthermore, statistical analysis revealed novel associations between various clinical measures of the PD subjects and the different fibroblast and neuronal data. In essence, these findings encapsulate spontaneous, in-tandem, disease-related phenotypes in both sporadic PD fibroblasts and iPSC-based DA neurons, from the same patient, and generates an innovative model to investigate PD mechanisms with a view towards rational disease stratification and precision treatments. 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/2022.12.24.521864v1?rss=1 Authors: Oberto, V., Matsumoto, J., Pompili, M. N., Todorova, R., Papaleo, F., Nishijo, H., Venance, L., Vandecasteele, M., Wiener, S. Abstract: Dopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNpc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates. We recorded from optogenetically identified dopaminergic sites in mice training in operant olfactory and visual discrimination tasks. Rayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1-2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals. These data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior. 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/2022.12.23.521819v1?rss=1 Authors: Meliss, S., Murayama, K. Abstract: Human memory is selective and not all experiences are remembered. Both monetary rewards/incentives and curiosity have been found to motivate and facilitate learning by dopaminergic midbrain projections to the hippocampus during encoding. In this study, we examined potential brain mechanisms during early consolidation period that jointly or independently contribute to these facilitating effects. Participants (N = 50) watched 36 videos of magic tricks and rated their "subjective feelings of curiosity" while the availability of extrinsic incentives was manipulated between groups. Functional magnetic resonance imaging (fMRI) data were acquired before, during, and after learning, and memory for magic tricks was assessed one week after. Our analysis focused on the change in resting-state functional connectivity (RSFC) between the dopaminergic midbrain and the anterior hippocampus, a dopaminergic consolidation mechanism previously reported in the context of extrinsically motivated learning. Changes in RSFC were correlated with behavioural measures of learning, i.e., the total number of items encoded and the curiosity-driven memory benefit. We found that brain-behaviour correlations differed depending on the availability of extrinsic incentives. More specifically, the correlation between the total number of items encoded and RSFC change was significantly different in the incentivised compared to the control group. The curiosity-driven memory benefit, however, did not correlate with changes in RSFC in either of the groups. In sum, this suggests that curiosity-motivated learning might be supported by different consolidation mechanisms compared to extrinsically motivated learning and that extrinsic incentives influence consolidation mechanisms supporting learning. 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/2022.12.21.521262v1?rss=1 Authors: Ali, M. A., Lischka, K., Preuss, S. J., Trivedi, C. A., Bollmann, J. H. Abstract: In motor control, the brain not only sends motor commands to the periphery, but it also generates concurrent internal signals known as corollary discharge that influence the processing of sensory information around the time of movement. Corollary discharge signals are important for the brain to identify sensory input arising from self-motion and to compensate for it, but the underlying mechanisms remain unclear. Using whole-cell patch clamp recordings from single neurons in the optic tectum of zebrafish, we discovered an inhibitory synaptic signal which was temporally locked to spontaneous and visually driven swim patterns. This motor-related synaptic signal transiently suppressed tectal output and was appropriately timed to counteract visually driven excitatory input arising from the fish's own motion. High-resolution calcium imaging revealed brief, highly localized post-swim signals in the tectal neuropil, suggesting that corollary discharge enters the tectum in its most superficial layer. Our results demonstrate how spurious visual input is suppressed during self-motion by motor-related phasic inhibition in the tectum. This may help explain perceptual saccadic suppression observed in many species. 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/2022.12.14.520294v1?rss=1 Authors: Sulzer, D., Hobson, B., Stanley, A., De Los Santos, M., Culbertson, B., Mosharov, E., Sims, P. Abstract: Dysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With the exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable in the mature, healthy central nervous system (CNS). Neurons have generally been considered incapable of antigen presentation, and although interferon gamma (IFN-{gamma}) can elicit neuronal MHC class I (MHC-I) expression and antigen presentation in vitro, it remains unclear whether similar responses occur in vivo. Here we directly injected IFN-{gamma} into the ventral midbrain of mature mice and analyzed gene expression profiles of specific CNS cell types. We find that IFN-{gamma} induces cellular proliferation and expression of MHC-II and associated genes only in microglia. However, IFN-{gamma} upregulated MHC-I and associated mRNAs in ventral midbrain microglia, astrocytes, oligodendrocytes, and GABAergic, glutamatergic, and dopaminergic neurons. The core set of IFN-{gamma}-induced genes and their response kinetics were conserved across neurons and glia, with a lower amplitude of expression in neurons. A diverse repertoire of genes was upregulated in glia, particularly microglia, while no neuron-specific responses to IFN-{gamma} were observed. Using mutant mice to selectively delete the IFN-{gamma}-binding domain of IFNGR1 in dopaminergic neurons, we demonstrate that dopaminergic neurons respond directly to IFN-{gamma}. Our results suggest that most neurons are capable of responding directly to IFN-{gamma} and upregulating MHC-I and related genes in vivo, but their expression amplitude and repertoire is limited compared to oligodendrocytes, astrocytes, and microglia. 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/2022.11.20.517243v1?rss=1 Authors: Land, R., Kral, A. Abstract: The extent to which aging of the central auditory pathway impairs auditory perception in the elderly independent of peripheral cochlear decline is debated. To cause auditory deficits in normal hearing elderly, central aging needs to degrade neural sound representations at some point along the auditory pathway. However, inaccessible to psychophysical methods, the level of the auditory pathway at which aging starts to effectively degrade neural sound representations remains poorly differentiated. Here we tested how potential age-related changes in the auditory brainstem affect the stability of spatiotemporal multiunit complex speech-like sound representations in the auditory midbrain of old normal hearing CBA/J mice. Although brainstem conduction speed slowed down in old mice, the change was limited to the sub-millisecond range and only minimally affected temporal processing in the midbrain (i.e. gaps-in-noise sensitivity). Importantly, besides the small delay, multiunit complex temporal sound representations in the auditory midbrain did not differ between young and old mice. This shows that although small age-related neural effects in simple sound parameters in the lower brainstem may be present in aging they do not effectively deteriorate complex neural population representations at the level of the auditory midbrain when peripheral hearing remains normal. This result challenges the widespread belief of pure central auditory decline as an automatic consequence of aging. However, the stability of midbrain processing in aging emphasizes the role of undetected 'hidden' peripheral damage and accumulating effects in higher cortical auditory-cognitive processing explaining perception deficits in 'normal hearing' elderly. 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/2022.11.11.516066v1?rss=1 Authors: Thomas, R. A., Sirois, J. M., Li, S., Gestin, A., Piscopo, V. E., Lepine, P., Mathur, M., Chen, C. X. Q., Soubannier, V., Goldsmith, T. M., Fawaz, L., Durcan, T. M., Fon, E. A. Abstract: With the recent surge of single cell RNA sequencing datasets (scRNAseq) the extent of cellular heterogeneity has become apparent, yet it remains poorly characterized on a protein level in brain tissue and induced pluripotent stem cell (iPSC) derived brain models. With this in mind, we developed a high-throughput, standardized approach for the reproducible characterization of cell types in complex neuronal tissues. We designed a flow cytometry (FC) antibody panel coupled with a computational pipeline to quantify cellular subtypes in human iPSC derived midbrain organoids. Our pipeline, termed CelltypeR, contains scripts to transform and align multiple datasets, optimize unsupervised clustering, annotate cell types, quantify cell types, and compare cells across conditions. We identified the expected brain cell types, then sorted neurons, astrocytes, and radial glia, confirming these cell types with scRNAseq. We present an adaptable analysis framework providing a generalizable method to reproducibly identify cell types across FC datasets. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
https://psychiatry.dev/wp-content/uploads/speaker/post-10749.mp3?cb=1668008421.mp3 Playback speed: 0.8x 1x 1.3x 1.6x 2x Download: Midbrain dopamine neurons arbiter OCD-like behavior – PubMed Jinwen Xue et al. PNAS. 2022. The neurobiological understanding of obsessive-compulsive disorder (OCD) includesFull EntryMidbrain dopamine neurons arbiter OCD-like behavior – PubMed
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.08.515628v1?rss=1 Authors: Grochowska, M. M., Ferraro, F., Carreras Mascaro, A., Natale, D., Winkelaar, A., Boumeester, V., Breedveld, G. J., Bonifati, V., Mandemakers, W. Abstract: Astrocytes are the most populous cell type of the human central nervous system and are essential for physiological brain function. Increasing evidence suggests multiple roles for astrocytes in Parkinson's disease (PD), nudging a shift in the research focus, which historically pivoted around the ventral midbrain dopaminergic neurons (vmDANs). Studying human astrocytes and other cell types in vivo remains technically and ethically challenging. However, in vitro reprogrammed human stem cell-based models provide a promising alternative. Here, we describe a novel protocol for astrocyte differentiation from human stem cell-derived vmDANs-generating progenitors. This protocol simulates the regionalization, gliogenic switch, radial migration, and final differentiation that occur in the developing human brain. We have characterized the morphological, molecular, and functional features of these ventral midbrain astrocytes with a broad palette of techniques. In addition, we have developed a new pipeline for calcium imaging data analysis called deCLUTTER2+ (deconvolution of Ca2+ fluorescent patterns) that can be used to discover spontaneous or cue-dependent patterns of Ca2+ transients. Altogether, our protocol enables the characterization of the functional properties of human ventral midbrain astrocytes under physiological conditions and in PD. 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/2022.11.05.515308v1?rss=1 Authors: Ibrahim, B. A., Shinagawa, Y., Xiao, G., Asilador, A. R., Llano, D. A. Abstract: The inferior colliculus (IC) is an information processing hub that receives widespread 25 convergent projections. It contains two non-lemniscal divisions - the dorsal (DC) and lateral (LC) 26 cortices - that receive major cortical and multisensory projections. The LC in particular has 27 repeated molecular motifs that govern its input-output relationships. However, because the LC 28 is buried deep within a sulcus, it has been impossible to study by imaging, and thus difficult to 29 answer questions about its functional organization. Here, we couple two-photon microscopy with use of a microprism to reveal the first-ever sagittal views containing functional maps of the LC with cellular resolution. We used this novel approach to examine neuronal responses with respect to LC motifs, and demonstrate the LC is functionally distinct from DC. This method will not only provide new insights about the auditory system, but will also permit imaging of hidden brain regions previously un-imageable by conventional means. 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/2022.10.30.514394v1?rss=1 Authors: Bhaskar, S., Gowda, J., Hegde, A., Thumu, S. C. R., Ramanan, N., Prasanna, J., KUMAR, A. Abstract: Dopaminergic (DA) neurons in the Olfactory bulb (OB) are involved in odor detection and discrimination. Transcription factor (TF) regulatory network responsible for their fate specification remains poorly understood and the spatial regulation of DA neurons remains elusive. In this study, mice exposed to odor stimulant exhibited specific upregulation of Zinc finger transcription factor of Cerebellum (ZIC) 3 along with Tyrosine Hydroxylase (TH). Stringent co-expression analysis showed ZIC3 and TH dual positive neurons in OB. Genetic manipulation showed ZIC3 to be both essential and sufficient to drive TH expression and essential for odor perception. ZIC3 interacts with ER81 and binds to region encompassing ER81 binding site in DA neurons and is indispensable for TH expression. In midbrain (MB), in the absence of ER81, ZIC3 switches its molecular partner and binds to Pitx3 promoter- a DA fate determinant. Under ectopic expression of ER81 in MB DA neurons, propensity of ZIC3 binding to Pitx3 promoter is compromised and its occupancy on Th promoter encompassing ER81 binding site is established, finally culminating in desired TH expression. Together, these findings reveal a unique ZIC3 mediated bimodal regulation of TH in OB and MB to ultimately facilitate DAergic fate. 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/2022.10.29.514341v1?rss=1 Authors: Rodrigues, T., Dib, L., Brethaut, E., Matter, M. M., Matter-Sadzinski, L., Matter, J.-M. Abstract: The increase of brain neuron number in relation with brain size is currently considered to be the major evolutionary path to high cognitive power in amniotes. However, how changes in neuron density did contribute to the evolution of the information-processing capacity of the brain remains unanswered. High neuron densities are seen as the main reason why the fovea located at the optical center of the retina is responsible for sharp vision in birds and primates. The emergence of foveal vision is considered as a breakthrough innovation in visual system evolution. We found that neuron densities in the largest visual center of the midbrain, i.e., the optic tectum, are two to four times higher in modern birds with one or two foveae compared to birds deprived of this specialty. Interspecies comparisons enabled us to identify elements of a hitherto unknown developmental process set up by foveate birds for increasing neuron density in the upper layers of their optic tectum. The progenitor cells that generate these neurons proliferate in a ventricular zone that can expand only radially. In this particular context, the number of cells in ontogenetic columns increases, thereby setting the conditions for higher cell densities in the upper layers once neurons did migrate. 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/2022.10.28.514238v1?rss=1 Authors: Virdi, G. S., Choi, M. L., Evans, J. R., Yao, Z., Athauda, D., Strohbuecker, S., Wernick, A. I., Alrashidi, H., Melandri, D., Perez-lloret, J., Stroh, P. R., Sylantyev, S., Eaton, S., Heales, S., Kunath, T., Horrocks, M. H., Abramov, A. Y., Patani, R., Gandhi, S. Abstract: Mutations in the SNCA gene cause autosomal dominant Parkinsons disease (PD), with progressive loss of dopaminergic neurons in the substantia nigra, and accumulation of aggregates of alpha-synuclein. However, the sequence of molecular events that proceed from the SNCA mutation during development, to its end stage pathology is unknown. Utilising human induced pluripotent stem cells (hiPSCs) with SNCA mutations, we resolved the temporal sequence of pathophysiological events that occur during neuronal differentiation in order to discover the early, and likely causative, events in synucleinopathies. We adapted a small molecule-based protocol that generates highly enriched midbrain dopaminergic (mDA) neurons ( greater than 80%). We characterised their molecular identity using single-cell RNA sequencing and their functional identity through the synthesis and secretion of dopamine, the ability to generate action potentials, and form functional synapses and networks. RNA velocity analyses confirmed the developmental transcriptomic trajectory of midbrain neural precursors into mDA neurons using our approach, and identified key driver genes in mDA neuronal development. To characterise the synucleinopathy, we adopted super-resolution methods to determine the number, size and structure of aggregates in SNCA-mutant mDA neurons. At one week of differentiation, prior to maturation to mDA neurons of molecular and functional identity, we demonstrate the formation of small aggregates; specifically, beta-sheet rich oligomeric aggregates, in SNCA-mutant midbrain immature neurons. The aggregation progresses over time to accumulate phosphorylated aggregates, and later fibrillar aggregates. When the midbrain neurons were functional, we observed evidence of impaired physiological calcium signalling, with raised basal calcium, and impairments in cytosolic and mitochondrial calcium efflux. Once midbrain identity fully developed, SNCA-mutant neurons exhibited bioenergetic impairments, mitochondrial dysfunction and oxidative stress. During the maturation of mDA neurons, upregulation of mitophagy and autophagy occured, and ultimately these multiple cellular stresses lead to an increase in cell death by six weeks post-differentiation. Our differentiation paradigm generates an efficient model for studying disease mechanisms in PD, and highlights that protein misfolding to generate intraneuronal oligomers is one of the earliest critical events driving disease in human neurons, rather than a late-stage hallmark of the disease. 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/2022.10.14.512269v1?rss=1 Authors: Zhu, X., Prakash, S. S., McAuliffe, G., Pan, P.-Y. Abstract: A major pathological hallmark of Parkinsons Disease (PD) is the manifestation of Lewy bodies comprised of alpha-synuclein (a-syn). The accumulation of a-syn enriched protein aggregates is thought to arise from dysfunction in degradation systems within the brain. Recently, missense mutations of SYNJ1 encoding the SAC1 and 5-phosphatase domains have been found in families with hereditary early-onset Parkinsonism. Previous studies showed that Synj1 haploinsufficiency (Synj1+/-) leads to PD-like behavioral and pathological changes in mice, including the accumulation of the autophagy substrate p62 and pathological a-syn proteins in the midbrain (MB) and striatum. In this study, we aim to investigate the neuronal degradation pathway using the Synj1+/- MB culture as a model. Our data suggests that autophagy flux and cumulative autophagosome formation is unaltered at baseline in Synj1+/- MB neurons. However, lysosome number is reduced with a similar decrease in lysosomal proteins, including LAMP1, LAMP2, and LAMP2A. Lysosomes are hyperacidified with enhanced enzymatic activity in Synj1+/- MB neurons. Using a combination of light and electron microscopy, we show that lysosomal changes are primarily associated with a lack of SAC1 activity. Consistently, expressing the SYNJ1 R258Q mutant in N2a cells reduces the lysosome number. Interestingly, the lysosomal defects in Synj1+/- neurons does not impact the clearance of exogenously expressed wild-type a-syn; however, the clearance of a-syn A53T was impaired in the axons of Synj1+/- MB neurons. Taken together, our results suggest axonal vulnerability to lysosomal defects in Synj1 deficient MB neurons. 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/2022.10.06.511202v1?rss=1 Authors: Chen, C., Ertman, A., de Hoz, L. Abstract: The acoustic context is ubiquitous, highly informative and often predictable. Yet, we know little about where and how contextual sounds are coded in the brain. We have some understanding about the coding of reinforced sounds in the auditory cortex and subcortical midbrain. Contextual sounds, however, are learned in an unsupervised (non-reinforced) manner. Here we measured plasticity in the auditory midbrain, a hub of incoming and feedback auditory input, and found that it reflected learning of contextual information in a manner that depended on the predictability of the sound-context association and not on reinforcement. We found broad frequency-specific shifts in tuning in auditory midbrain neurons. These shifts were paralleled by an increase in response gain and correlated with an increase in neuronal frequency discrimination. The auditory midbrain, thus, codes for predictable and unsupervised sound-context associations. This points to a subcortical engagement in the detection of contextual sounds, a detection that facilitates the processing of relevant information described to occur in cortical auditory structures. 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/2022.09.29.510116v1?rss=1 Authors: Shadron, K. K., Pena, J. L. Abstract: Sensory systems display capability to preferentially choose stimuli based on their reliability at conveying accurate information. While previous reports have shown the ability of the brain to reweigh cues based on ongoing or dynamic changes in reliability, how the brain may learn and maintain neural responses to sensory statistics expected to be stable over longer time periods remain significant open questions of potential mechanisms underlying naturalistic biased perception. This study provides evidence that the barn owl's midbrain is shaped by permanent statistics experienced during development. The barn owl's midbrain features a topographic map of auditory space where neurons compute horizontal sound location from the interaural time difference (ITD). Previous work has shown that frequency tuning of these midbrain map neurons is correlated with the pattern of most reliable frequencies for the neurons' preferred ITD. This pattern of ITD reliability is due to the filtering properties of the head, primarily determined by the facial ruff in the barn owl. In this study, we found that the absence of a facial ruff led to a decrease in the reliability of high frequencies originating from frontal space. To test if the owl's frequency tuning of midbrain map neurons is driven by permanent changes in the pattern of ITD reliability, these neurons were recorded from adult owls, who had the facial ruff removed as juveniles, and from juvenile owls, before the facial ruff developed. In both groups, we found that frontally-tuned neurons displayed tunings to frequencies lower than reported in normal adult owls, consistent with the difference in ITD reliability between the normal and ruff removed conditions. Juvenile owls also exhibited more heterogeneous frequency tuning, suggesting developmental processes that refine tuning to match the pattern of ITD reliability. Additional recordings immediately upstream of the midbrain map displayed ITD tuned neural responses for all frequencies across the owl's normal hearing range. Broader analysis of the effects of ruff-removal on the acoustical properties of spatial cues indicated a dominant role of ITD reliability in driving the adaptive changes in frequency tuning. These results support the hypothesis that frequency tuning in the midbrain map is developmentally adapted to permanent statistics of spatial cues, implementing probabilistic coding for sound localization. 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/2022.09.15.507987v1?rss=1 Authors: Nishimura, K., Yang, S., Lee, K., Asgrimsdottir, E. S., Nikouei, K., Paslawski, W., Gnodde, S., Lyu, G., Hu, L., Salto, C., Svenningsson, P., Hjerling-Leffler, J., Linnarsson, S., Arenas, E. Abstract: Stem cell technologies provide new opportunities for modeling cells in the healthy and diseased states and for regenerative medicine. In both cases developmental knowledge as well as the quality and molecular properties of the cells are essential for their future application. In this study we identify developmental factors important for the differentiation of human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons. We found that Laminin-511, and dual canonical and non-canonical WNT activation followed by GSK3b inhibition plus FGF8b, improved midbrain patterning. In addition, mDA neurogenesis and differentiation was enhanced by activation of liver X receptors and inhibition of fibroblast growth factor signaling. Moreover, single-cell RNA-sequencing analysis revealed a developmental dynamics similar to that of the endogenous human ventral midbrain and the emergence of high quality molecularly-defined midbrain cell types, including mDA neurons that become functional. Thus, our study identifies novel factors important for human midbrain development and opens the door for a future application of molecularly-defined hESC-derived midbrain cell types in Parkinsons disease. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.26.505472v1?rss=1 Authors: Morrone Parfitt, G., Coccia, E., Goldman, C., Whitney, K., Reyes, R., Sarrafha, L., Nam, K. H., Jones, D., crary, J. F., Ordureau, A., Blanchard, J., Ahfeldt, T. D. Abstract: Accumulation of advanced glycation end products (AGEs) on biopolymers accompany cellular aging and drives poorly understood disease processes. Here, we studied how AGEs contribute to development of early on-set Parkinson's Disease (PD) caused by loss-of-function of DJ1, a protein deglycase. In induced pluripotent stem cell (iPSC)-derived midbrain organoid models deficient for DJ1 activity, we find that lysosomal proteolysis is impaired, causing AGEs to accumulate, -synuclein (-syn) phosphorylation to increase, and proteins to aggregate. These processes are at least partly driven by astrocytes, as DJ1 loss reduces their capacity to provide metabolic support and triggers acquisition of a pro-inflammatory phenotype. Consistently, in co-cultures, we find that DJ1-expressing astrocytes are able to reverse the proteolysis deficits of DJ1 knockout midbrain neurons. In conclusion, astrocytes' capacity to clear toxic damaged proteins is critical to preserve neuronal function and their dysfunction contributes to the neurodegeneration observed in PD. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Su-Chun Zhang, M.D., Ph.D., shares how neural transplantation cell therapies can be used to treat neurological conditions such as Parkinson's disease. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 38203]
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.08.24.505113v1?rss=1 Authors: Larbi, M. C., Messa, G., Jalal, H., Koutsikou, S. Abstract: Vertebrate locomotion is heavily dependent on descending control originating in the midbrain and subsequently influencing central pattern generators in the spinal cord. However, the midbrain neuronal circuitry and its connections with other brainstem and spinal motor circuits has not been fully elucidated. Basal vertebrates with very simple nervous system, like the hatchling Xenopus laevis tadpole, have been instrumental in unravelling fundamental principles of locomotion and its suspraspinal control. Here, we use behavioral and electrophysiological approaches in combination with lesions of the midbrain to investigate its contribution to the initiation and control of the tadpole swimming in response to trunk skin stimulation. None of the midbrain lesions studied here blocked the tadpole's sustained swim behavior following trunk skin stimulation. However, we identified that distinct midbrain lesions led to significant changes in the latency and trajectory of swimming. These changes could partly be explained by the increase in synchronous muscle contractions on the opposite sides of the tadpole's body and permanent deflection of the tail from its normal position, respectively. Furthermore, the midbrain lesions led to significant changes in the tadpole's ability to stop swimming when it bumps head on to solid objects. We conclude that the tadpole's embryonic trunk skin sensorimotor pathway involves the midbrain, which harbors essential neuronal circuitry to significantly contribute to the appropriate, timely and coordinated selection and execution of locomotion, imperative to the animal's survival. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
The Midbrain is BACK by Evan
Yup...halfway through season 2 - and still no live Scrabble tournaments. Meh! Well why not study something a lil different today...the MID and MIS uncommon prefixes. It's not like you're MIS-sing anything else to do yet.... | MIDAIRS | | MIDCULT | | MIDDENS | | MIDDIES | | MIDDLER | | MIDGUTS | | MIDIRON | | MIDLEGS | | MIDLINE | | MIDLIST | | MIDNOON | | MIDRASH | | MIDRIBS | | MIDSOLE | | MIDBRAIN | | MIDLIFER | | MIDMOSTS | | MIDSPACE | | MIDSTORY | | MIDWATCH | | MIDWATER | | MIDWIFED | MIDWIVE MIDWIFED | | | MISAIMS | | MISALLY | | MISAVER | | MISBIAS | | MISBIND | | MISCITE | | MISCODE | | MISCOIN | | MISCOOK | | MISCUED | | MISDEEM | | MISCUTS | | MISDRAW | MISDREW | MISEASE | | MISEATS | | MISEDIT | | MISFORM | | MISGAGE | MISGAUGE | MISHITS | | MISJOIN | | MISKALS | | MISKICK | | MISKNOW | MISNEW MISKNOWN` | MISLIES | | MISLIKE | | MISLIVE | | MISMOVE | | MISPAGE | | MISPART | | MISPENS | | MISPLAN | | MISPLED | | MISRATE | | MISRELY | | MISSALS | | MISSELS | | MISSETS | | MISSHOD | | MISTEUK | | MISTUNE | | MISWORD | | MISWRIT | | MISYOKE | | MISTBOW | | MISAGENT | | MISALTER | | MISBEGOT | | MISAWARD | | MISCIBLE | | MISENROL | | MISERERE | | MISEVENT | | MISFAITH | | MISFOCUS | | MISFRAME | | MISGIVES | | MISHMASH | MISHMOSH | MISINFER | | MISINTER | | MISLABOR | | MISLAYER | | MISLIKER | | MISLODGE | | MISMATED | | MISOGAMY | | MISOGANY | | MISOLOGY | | MISPAINT | | MISPRIZE | | MISPOISE | | MISREFER | | MISSENSE | | MISSOUND | | MISSPELT | MISSPELLED | MISSTAMP | | MISSTEER | | MISSTOPS | | MISSUITS | | MISTAKER | | MISTITLE | | MISTRACE | | MISTRYST | | MISTUTOR | | MISUNION | | MISUSERS |
It is a question in Psychology and Neuroscience how people who are constantly adventurous and rigidly stuck to what they know are both using the dopamine systems found in the midbrain. How can two seemingly opposite patterns of behaviour come from the same source and why whenever a discussion about the brain starts is it always somehow focused on dopamine. Michael J Frank is an expert on the dopamine systems in the human brain and brings his research and decades of experience to help us understand what the dopamine system is actually doing here. This show is sponsored by NeuroCatch Inc., an objective quick measure of brain health available today. If you would like to know more about NeuroCatch Inc. please go to our website www.watercoolerneuroscience.co.uk.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.20.392175v1?rss=1 Authors: Tokarew, J. M., El Kodsi, D. N., Lengacher, N. A., Fehr, T. K., Nguyen, A. P., Shutinoski, B., O'Nuallain, B., Jin, M., Khan, J., Ng, A. C. H., Li, J., Jiang, Q., Zhang, M., Wang, L., Sengupta, R., Barber, K., Tran, A., Zandee, S., Dong, X., Scherzer, C. R., Prat, A., Tsai, E., Takanashi, M., Hattori, N., Chan, J. A., Zecca, L., West, A., Holmgren, A., Puente, L., Shaw, G. S., Toth, G., Woulfe, J., Taylor, P., Tomlinson, J. J., Schlossmacher, M. G. Abstract: The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions, which are reflected in its posttranslational modifications. We found that in human control brain, including the S. nigra, parkin is largely insoluble after age 40 years, which is linked to its oxidation, e.g., at Cys95 and Cys253. In mice, oxidative stress increases posttranslational modifications at parkin cysteines and reduces its solubility. Oxidation of recombinant parkin also promotes insolubility and aggregate formation, but in parallel, lowers hydrogen peroxide (H2O2). This thiol-based redox activity is diminished by parkin point mutants, e.g., p.C431F and p.G328E. Intriguingly, in parkin-deficient human brain H2O2 concentrations are elevated. In prkn-null mice, H2O2 levels are dysregulated under oxidative stress conditions, such as acutely by MPTP-toxin exposure or chronically due to a second genetic hit. In dopamine toxicity studies, wild-type parkin, but not disease-linked mutants, protects human dopaminergic M17 cells, in part through lowering H2O2. Parkin also neutralizes reactive, electrophilic dopamine metabolites via adduct formation, which occurs foremost at primate-specific Cys95. Further, wild-type but not p.C95A-mutant parkin augments melanin formation. In sections of normal, adult human midbrain, parkin specifically co-localizes with neuromelanin pigment, frequently within LAMP-3/CD63+ lysosomes. We conclude that oxidative modifications of parkin cysteines are associated with protective outcomes, which include the reduction of H2O2, conjugation of reactive dopamine metabolites, sequestration of radicals within insoluble aggregates, and increased melanin formation. The loss of these redox effects may augment oxidative stress in dopamine producing neurons of mutant PRKN allele carriers, thereby contributing to neurodegeneration. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.17.384651v1?rss=1 Authors: Joshi, A., Faivre, F., la Fleur, S. E., Barrot, M. Abstract: Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we did 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. The food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinson's disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particularly the intake of fat. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.29.360750v1?rss=1 Authors: Ehrlich, I., Aksoy-Aksel, A., Gall, A., Seewald, A., Ferraguti, F. Abstract: Dopaminergic signaling plays an important role in associative learning including fear and extinction learning. Dopaminergic midbrain neurons encode prediction error-like signals when threats differ from expectations. Within the amygdala, GABAergic intercalated cell (ITC) clusters receive the densest dopaminergic projections, but their physiological consequences are incompletely understood. ITCs are important for fear extinction, a function thought to be supported by activation of ventromedial cluster ITCs that inhibit central amygdala fear output. In mice, we reveal two distinct mechanisms how mesencephalic dopaminergic afferents control ITCs. Firstly, they co-release GABA to mediate rapid, direct inhibition. Secondly, dopamine suppresses inhibitory interactions between distinct ITC clusters via presynaptic D1-receptors. Early extinction training augments both, GABA co-release onto dorso-medial ITCs and dopamine-mediated suppression of dorso- to ventromedial inhibition between ITC clusters. These findings provide novel insights into dopaminergic mechanisms shaping the activity balance between distinct ITC clusters that could support their opposing roles in fear behavior. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.09.333435v1?rss=1 Authors: Schaan Profes, M., Saghatelyan, A., Levesque, M. Abstract: Mesodiencephalic dopamine (mDA) neurons play a wide range of brain functions. Distinct subtypes of mDA neurons regulate these functions but the molecular mechanisms that drive the mDA circuit formation are largely unknown. Here we show that autophagy, the main recycling cellular pathway, is present in the growth cones of developing mDA neurons and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth/guidance, we knocked-out (KO) essential autophagy genes (Atg12, Atg5) in mice mDA neurons. Autophagy deficient mDA axons exhibit axonal swellings and decreased branching both in vitro and in vivo, likely due to aberrant microtubule looping. Strikingly, deletion of autophagy-related genes, blunted completely the response of mDA neurons to chemorepulsive and chemo-attractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neurons development, orchestrating axonal growth and guidance. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.01.322495v1?rss=1 Authors: Birtele, M., Sharma, Y., Storm, P., Kajtez, J., Sozzi, E., Nilsson, F., Nelander Wahlestedt, J., Stott, S., L He, X., Mattsson, B., Rylander Ottosson, D., Barker, R. A., Fiorenzano, A., Parmar, M. Abstract: Transplantation of midbrain dopamine (DA) neurons for the treatment of Parkinson s disease (PD) is a strategy that has being extensively explored and clinical trials using fetal and stem cell-derived DA neurons are ongoing. An increased understanding of the mechanisms promoting the generation of distinct subtypes of midbrain DA during normal development will be essential for guiding future efforts to precisely generate molecularly defined and subtype specific DA neurons from pluripotent stem cells. In this study, we used droplet-based scRNA-seq to transcriptionally profile a large number of fetal cells from human embryos at different stages of ventral midbrain (VM) development (6, 8, and 11 weeks post conception). This revealed that the emergence of transcriptionally distinct cellular populations was evident already at these early timepoints. To study late events of human DA differentiation and functional maturation, we established a primary fetal 3D culture system that recapitulates key molecular aspects of late human DA neurogenesis and sustains differentiation and functional maturation of DA neurons in a physiologically relevant cellular context. This approach allowed us to define the molecular identities of distinct human DA progenitors and neurons at single cell resolution and construct developmental trajectories of cell types in the developing fetal VM. Overall these findings provide a unique transcriptional profile of developing fetal VM and functionally mature human DA neurons, which can be used to quality control stem cell-derived DA neurons and guide stem cell-based therapies and disease modeling approaches in PD. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.16.300723v1?rss=1 Authors: Wang, Y., Toyoshima, O., Kunimatsu, J., Yamada, H., Matsumoto, M. Abstract: Appropriate actions are taken based on the values of future rewards. The phasic activity of midbrain dopamine neurons signals these values. Because reward values often change over time, even on a subsecond-by-subsecond basis, appropriate action selection requires continuous value monitoring. However, the phasic dopamine activity, which is sporadic and has a short duration, likely fails continuous monitoring. Here, we demonstrate a tonic firing mode of dopamine neurons that effectively tracks changing reward values. We recorded dopamine neuron activity in monkeys during a Pavlovian procedure in which the value of a cued reward gradually increased or decreased. Dopamine neurons tonically increased and decreased their activity as the reward value changed. This tonic activity was evoked more strongly by non-burst spikes than burst spikes producing a conventional phasic activity. Our findings suggest that dopamine neurons change their firing mode to effectively signal reward values, which could underlie action selection in changing environments. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.08.287797v1?rss=1 Authors: Virdi, G. S., Choi, M. L., Yao, Z., Evans, J. R., Athauda, D., Melandri, D., Sylantyev, S., Abramov, A. Y., Patani, R., Gandhi, S. Abstract: The development of human induced pluripotent stem cells (hiPSC) has greatly aided our ability to model neurodegenerative diseases. However, generation of midbrain dopaminergic (mDA) neurons is a major challenge and protocols are variable. Here, we developed a method to differentiate hiPSCs into enriched populations (>80%) of mDA neurons using only small molecules. We confirmed the identity of the mDA neurons using single-cell RNA-sequencing and detection of classical markers. Single-cell live imaging demonstrated neuronal calcium signalling and functional dopamine transport. Electrophysiology measures highlighted the ability to form synapses and networks in culture. Patient-specific hiPSC lines differentiated to produce functional mDA neurons that exhibit the hallmarks of synucleinopathy including: aggregate formation, oxidative stress as well as mitochondrial dysfunction and impaired lysosomal dynamics. In summary, we establish a robust differentiation paradigm to generate enriched mDA neurons from hiPSCs, which can be used to faithfully model key aspects of Parkinson's disease (PD), providing the potential to further elucidate molecular mechanisms contributing to disease development. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.02.279380v1?rss=1 Authors: Kinugawa, K., Luginbühl, J., Matsui, T. K., Eura, N., Sakaguchi, Y. M., Shin, J. W., Sugie, K., Schwamborn, J. C., Mori, E. Abstract: Human brain organoids provide us the means to investigate human brain development and neurological diseases, and single-cell RNA-sequencing (scRNA-seq) technologies allow us to identify homologous cell types and the molecular heterogeneity between individual cells. Previously established human brain organoids of brainstem (hBSOs) and midbrain (hMBOs) were analyzed by scRNA-seq, but the difference in cellular composition between these organoids remains unclear. Here, we integrated and compared the single-cell transcriptome of hBSOs and hMBOs. Our analysis demonstrated that the hBSOs and hMBOs contain some unique cell types, including inflammatory and mesenchymal cells. Further comparison of the hBSOs and hMBOs with publicly available scRNA-seq dataset of human fetal midbrain (hMB) showed high similarity in their neuronal components. These results provide new insights into human brain organoid technologies. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.21.260422v1?rss=1 Authors: Trevizan Bau, P., Dhingra, R. R., Furuya, W. I., Stanic, D., Mazzone, S. B., Dutschmann, M. Abstract: Eupnea is generated by neural circuits located in the ponto-medullary brainstem, but can be modulated by higher brain inputs which contribute to volitional control of breathing and the expression of orofacial behaviors, such as vocalization, sniffing, coughing and swallowing. Surprisingly, the anatomical organization of descending inputs that connect the forebrain with the brainstem respiratory network remains poorly defined. We hypothesized that descending forebrain projections target multiple distributed respiratory control nuclei across the neuraxis. To test our hypothesis, we made discrete unilateral microinjections of the retrograde tracer Cholera toxin subunit B (CT-B) in the midbrain periaqueductal gray (PAG), the pontine Kolliker-Fuse nucleus (KFn), the medullary Botzinger complex (BotC), pre-Botzinger complex (pre-BotC) or caudal midline raphe nuclei. We quantified the regional distribution of retrogradely-labeled neurons in the forebrain 12-14 days post-injection. Overall, our data reveals that descending inputs from cortical areas predominantly target the PAG and KFn. Differential forebrain regions innervating the PAG (prefrontal, cingulate cortices, and lateral septum) and KFn (rhinal, piriform, and somatosensory cortices) imply that volitional motor commands for vocalization are specifically relayed via the PAG, while the KFn may receive commands to coordinate breathing with other orofacial behaviors (e.g. sniffing, swallowing). Additionally, we observed that the limbic or autonomic (interoceptive) systems are connected to broadly distributed downstream bulbar respiratory networks. Collectively, these data provide a neural substrate to explain how volitional, state-dependent, and emotional modulation of breathing is regulated by the forebrain. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.14.251546v1?rss=1 Authors: Huerta-Ocampo, I., Dautan, D., Gut, N. K., Khan, B., Mena-Segovia, J. Abstract: The cholinergic midbrain is involved in a wide range of motor and cognitive processes. Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental nucleus (LDT) send long-ranging axonal projections that target sensorimotor and limbic areas in the thalamus, the dopaminergic midbrain and the striatal complex following a topographical gradient, where they influence a range of functions including attention, reinforcement learning and action-selection. Nevertheless, a comprehensive examination of the afferents to PPN and LDT cholinergic neurons is still lacking, partly due to the neurochemical heterogeneity of this region. Here we characterize the whole-brain input connectome to cholinergic neurons across distinct functional domains (i.e. PPN vs LDT) using conditional transsynaptic retrograde labeling in ChAT::Cre male and female rats. The quantification of input neurons revealed that both PPN and LDT receive similar substantial inputs from the superior colliculus and the output of the basal ganglia (i.e. substantia nigra pars reticulata). In addition, we found that PPN cholinergic neurons receive preferential inputs from basal ganglia structures than from the cortex, whereas LDT cholinergic neurons receive preferential inputs from cortical areas. Our results provide the first characterization of inputs to PPN and LDT cholinergic neurons. The differences in afferents to each cholinergic structure support their differential roles in behavior. Copy rights belong to original authors. Visit the link for more info
Diving into Oran Klaff’s incredible book Pitch Anything. My personal favorite book in sales and persuasion which focuses on how we evoke change on a neurological level. This is the first of our two part series on this game changing book book. Highly recommend you pick up a copy today!: Pitch Anything: An Innovative Method for Presenting, Persuading, and Winning the Deal https://www.amazon.com/dp/0071752854/ref=cm_sw_r_cp_api_i_A9ekFbDBXG6MD --- Send in a voice message: https://anchor.fm/mdrnac/message
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.24.219246v1?rss=1 Authors: Miozzo, F., Stickley, L., Tas, D., Loncle, N., Nikonenko, I., Dorcikova, M., Valencia-Alarcon, E. P., Bou Dib, P., Nagoshi, E. Abstract: The degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson's Disease (PD). Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. We further show that conditional ablation of Nato3, a mouse homolog of Fer2, in differentiated DA neurons results in locomotor impairments and mitochondrial abnormality in aged mice. Our results reveal the essential and conserved role of Fer2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modelling and treating PD. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.22.164814v1?rss=1 Authors: Chen, R., Gadagkar, V., Roeser, A. C., Puzerey, P. A., Goldberg, J. H. Abstract: Movement-related neuronal discharge in ventral tegmental area (VTA) and ventral pallidum (VP) is inconsistently observed across studies. One possibility is that some neurons are movement-related and others are not. Another possibility is that the precise behavioral conditions matter - that a single neuron can be movement related under certain behavioral states but not others. We recorded single VTA and VP neurons in birds transitioning between singing and non-singing states, while monitoring body movement with microdrive-mounted accelerometers. Many VP and VTA neurons exhibited body movement-locked activity exclusively when the bird was not singing. During singing, VP and VTA neurons could switch off their tuning to body movement and become instead precisely time-locked to specific song syllables. These changes in neuronal tuning occurred rapidly at state boundaries. Our findings show that movement-related activity in limbic circuits can be gated by behavioral context. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.16.154740v1?rss=1 Authors: Fullerton, E. F., Rubaharan, M., Karom, M. C., Hanberry, R. L., Murphy, A. Z. Abstract: The present study investigated the impact of advanced age on morphine modulation of persistent inflammatory pain in male and female rats. The impact of age, sex, and pain on mu-opioid receptor (MOR) expression and binding in the ventrolateral PAG (vlPAG) was also examined using immunohistochemistry and receptor autoradiography. Intraplantar administration of Complete Freund's adjuvant induced comparable levels of edema and hyperalgesia in adult (2-3mos) and aged (16-18mos) male and female rats. Morphine potency was highest in adult males, with a two-fold decrease in morphine EC50 observed in aged versus adult males (10.22mg/kg versus 5.19mg/kg). Adult and aged female rats also exhibited significantly higher EC50 values (10.69 mg/kg and 9.00 mg/kg, respectively) compared to adult males. The upward shift in EC50 from adult to aged males was paralleled by a reduction in vlPAG MOR expression and binding. The observed age-related reductions in morphine potency and vlPAG MOR expression and binding have significant implications in pain management in the aged population. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.16.155432v1?rss=1 Authors: Saderi, D., Schwartz, Z. P., Heller, C. R., Pennington, J. R., David, S. V. Abstract: The brain's representation of sound is influenced by multiple aspects of internal behavioral state. Following engagement in an auditory discrimination task, both generalized arousal and task-specific control signals can influence auditory processing. To isolate effects of these state variables on auditory processing, we recorded single-unit activity from primary auditory cortex (A1) and the inferior colliculus (IC) of ferrets as they engaged in a go/no-go tone detection task while simultaneously monitoring arousal via pupillometry. We used a generalized linear model to isolate the contributions of task engagement and arousal on spontaneous and evoked neural activity. Fluctuations in pupil-indexed arousal were correlated with task engagement, but these two variables could be dissociated in most experiments. In both A1 and IC, individual units could be modulated by task and/or arousal, but the two state variables affected independent neural populations. Arousal effects were more prominent in IC, while arousal and engagement effects occurred with about equal frequency in A1. These results indicate that some changes in neural activity attributed to task engagement in previous studies should in fact be attributed to global fluctuations in arousal. Arousal effects also explain some persistent changes in neural activity observed in passive conditions post-behavior. Together, these results indicate a hierarchy in the auditory system, where generalized arousal enhances activity in the midbrain and cortex, while task-specific changes in neural coding become more prominent in cortex. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.04.134478v1?rss=1 Authors: Lauter, G., Coschiera, A., Yoshihara, M., Sugiaman-Trapman, D., Ezer, S., Sethurathinam, S., Katayama, S., Kere, J., Swoboda, P. Abstract: Many human cell types are ciliated, including neural progenitors and differentiated neurons. Ciliopathies are characterized by defective cilia and comprise various disease states, including brain phenotypes, where the underlying biological pathways are largely unknown. Our understanding of neuronal cilia is rudimentary and an easy-to-maintain, ciliated human neuronal cell model is missing. LUHMES is a ciliated neuronal cell line derived from human fetal mesencephalon. LUHMES cells can easily be maintained and differentiated into mature, functional neurons within one week. They have a single primary cilium as proliferating progenitor cells and as post-mitotic, differentiating neurons. These developmental stages are completely separable within one day of culture condition change. The Sonic Hedgehog (SHH) signaling pathway is active in differentiating LUHMES neurons. RNA-seq time course analyses reveal molecular pathways and gene-regulatory networks critical for ciliogenesis and axon outgrowth at the interface between progenitor cell proliferation, polarization and neuronal differentiation. Gene expression dynamics of cultured LUHMES neurons faithfully mimic the corresponding in vivo dynamics of human fetal midbrain. In LUHMES, neuronal cilia biology can be investigated along a complete timeline: from proliferation through differentiation to mature neurons. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.31.126359v1?rss=1 Authors: Buonocore, A., Baumann, M. P., Hafed, Z. M. Abstract: At any moment in time, new information is sampled from the environment and interacts with ongoing brain state. Often, such interaction takes place within individual circuits that are capable of both mediating the internally ongoing plan as well as representing exogenous sensory events. Here we investigated how sensory-driven neural activity can be integrated, very often in the same neuron types, into ongoing oculomotor commands for saccades. Despite the ballistic nature of saccades, visually-induced action potentials in the superior colliculus (SC), a structure known to drive eye movements, not only occurred intra-saccadically, but they were also associated with highly predictable modifications of the ongoing eye movements. Such modifications were also possible by peri-saccadically injecting single, double, or triple electrical microstimulation pulses into the SC. Our results suggest instantaneous readout of the SC map during movement generation, irrespective of activity source, and explain a significant component of kinematic variability of motor outputs. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.21.108886v1?rss=1 Authors: Guru, A., Seo, C., Post, R. J., Kullakanda, D. S., Schaffer, J. A., Warden, M. R. Abstract: Journeys to novel and familiar destinations employ different navigational strategies. The first drive to a new restaurant relies on map-based planning, but after repeated trips the drive is automatic and guided by local environmental cues. Ventral striatal dopamine rises during navigation toward goals and reflects the spatial proximity and value of goals, but the impact of experience, the neural mechanisms, and the functional significance of dopamine ramps are unknown. Here, we used fiber photometry to record the evolution of activity in midbrain dopamine neurons as mice learned a variety of reward-seeking tasks, starting recordings before training had commenced and continuing daily for weeks. When mice navigated through space toward a goal, robust ramping activity in dopamine neurons appeared immediately - after the first rewarded trial on the first training day in completely naive animals. In this task spatial cues were available to guide behavior, and although ramps were strong at first, they gradually faded away as training progressed. If instead mice learned to run a fixed distance on a stationary wheel for reward, a task that required an internal model of progress toward the goal, strong dopamine ramps persisted indefinitely. In a passive task in which a visible cue and reward moved together toward the mouse, ramps appeared and then faded over several days, but in an otherwise identical task with a stationary cue and reward ramps never appeared. Our findings provide strong evidence that ramping activity in midbrain dopamine neurons reflects the use of a cognitive map - an internal model of the distance already covered and the remaining distance until the goal is reached. We hypothesize that dopamine ramps may be used to reinforce locations on the way to newly-discovered rewards in order to build a graded ventral striatal value landscape for guiding routine spatial behavior. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.13.093492v1?rss=1 Authors: Truong, P., Kim, J. H., Savjani, R., Sitek, K. R., Hagberg, G., Scheffler, K., Ress, D. Abstract: Dorsal human midbrain contains two nuclei with clear laminar organization, the superior and inferior colliculi. These nuclei extend in depth between the superficial dorsal surface of midbrain and a deep midbrain nucleus, the periaqueductal gray matter (PAG). The PAG, in turn, surrounds the cerebral aqueduct (CA). This study examined the use of two depth metrics to characterize depth and thickness relationships within dorsal midbrain using the superficial surface of midbrain and CA as references. The first utilized nearest-neighbor Euclidean distance from one reference surface, while the second used a level-set approach that combines signed distance from both reference surfaces. Both depth methods provided similar functional depth profiles generated by saccadic eye movements in a functional MRI task, confirming their efficacy for superficial functional activity. Next, the boundaries of the PAG were estimated using Euclidean distance together with elliptical fitting, indicating that the PAG can be readily characterized by a smooth surface surrounding PAG. Finally, we used the level-set approach to measure tissue depth between the superficial surface and the PAG, thus characterizing the variable thickness of the colliculi. Overall, this study demonstrates depth-mapping schemes for human midbrain that enables accurate segmentation of the PAG and consistent depth and thickness estimates of the superior and inferior colliculi. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.11.089078v1?rss=1 Authors: De Miranda, B. R., Rocha, E. M., Castro, S., Greenamyre, J. T. Abstract: Dopaminergic neurons of the substantia nigra are selectively vulnerable to mitochondrial dysfunction, which is hypothesized to be an early and fundamental pathogenic mechanism in Parkinson's disease (PD). Mitochondrial function depends on the successful import of nuclear-encoded proteins, many of which are transported through the TOM20-TOM22 outer mitochondrial membrane import receptor machinery. Recent data suggests that post-translational modifications of -synuclein promote its interaction with TOM20 at the outer mitochondrial membrane and thereby inhibit normal protein import, which leads to dysfunction and death of dopaminergic neurons. As such, preservation of mitochondrial import in the face of -synuclein accumulation might be a strategy to prevent dopaminergic neurodegeneration, however, this is difficult to assess using current in vivo models of PD. To this end, we established an exogenous co-expression system, utilizing AAV2 vectors to overexpress human -synuclein and TOM20, individually or together, in the adult Lewis rat substantia nigra in order to assess whether TOM20 overexpression attenuates -synuclein-induced dopaminergic neurodegeneration. Twelve weeks after viral injection, we observed that AAV2-TOM20 expression was sufficient to prevent loss of nigral dopaminergic neurons caused by AAV2-Syn overexpression. The observed TOM20-mediated dopaminergic neuron preservation appeared to be due, in part, to the rescued import of nuclear-encoded mitochondrial electron transport chain proteins that were inhibited by -synuclein overexpression. In addition, TOM20 overexpression rescued the import of the chaperone protein GRP75/mtHSP70/mortalin, a stress-response protein involved in -synuclein-induced injury. Collectively, these data indicate that TOM20 expression prevents -synuclein-induced mitochondrial dysfunction, which is sufficient to rescue dopaminergic neurons in the adult rat brain. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.01.071977v1?rss=1 Authors: Sarno, S., Beiran, M., Diaz-deLeon, G., Rossi-Pool, R., Romo, R., Parga, N. Abstract: Little is known about how dopamine (DA) neuron firing rates behave in cognitively demanding decision-making tasks. We investigated midbrain DA activity in monkeys performing a vibrotactile frequency discrimination task that required comparing two frequencies presented sequentially in time. We found that DA activity was involved in reward prediction, motivation and working memory (WM). Further, DA phasic responses to the stimuli were greatly affected by a contraction bias. They were also related to motivated behavior on a trial-by-trial basis, exhibiting a larger engagement in more difficult trials. Otherwise, dopamine WM activity was neither tuned to the initial stored frequency nor affected by the bias, although it did code the motivation level and exhibited a ramp-like increase. This result is consistent with a DA role in stabilizing sustained activity, by increasing the gain of prefrontal neurons in a motivation-dependent way. All these DA responses could be potentially related to cognitive control. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.28.063347v1?rss=1 Authors: Radlicka, A., Kaminska, K., Borczyk, M., Piechota, M., Korostynski, M., Pera, J., Lorenc-Koci, E., Rodriguez Parkitna, J. Abstract: The development of Parkinson's disease (PD) causes dysfunction of the frontal cortex, which contributes to hallmark motor symptoms and is regarded as one of the primary causes of the affective and cognitive impairments observed in PD. Treatment with L-DOPA alleviates motor symptoms but has mixed efficacy in restoring normal cognitive functions, which is further complicated by the psychoactive effects of the drug. In this study, we investigated how L-DOPA affects gene expression in the frontal cortex in an animal model of unilateral PD. We performed an RNA-seq analysis of gene expression in the frontal cortex of rats with 6-hydroxydopamine (6-OHDA)-induced unilateral dopaminergic lesion that were treated with L-3,4-dihydroxyphenylalanine (L-DOPA) , for 2 weeks. We used analysis of variance to identify differentially expressed genes and found 48 genes with significantly altered transcript abundance after L-DOPA treatment. We also performed a weighted gene coexpression network analysis (WGCNA), which resulted in the detection of 5 modules consisting of genes with similar expression patterns. The analyses led to three primary observations. First, the changes in gene expression induced by L-DOPA were bilateral, although only one hemisphere was lesioned. Second, the changes were not restricted to neurons but also appeared to emerge in immune or endothelial cells. Finally, comparisons with databases of drug-induced gene expression signatures revealed multiple nonspecific effects, which indicates that a part of the observed response is a common pattern activated by multiple types of pharmaceuticals in different target tissues. Taken together, our results identify cellular mechanisms in the frontal cortex that are involved in the response to L-DOPA treatment. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.27.053470v1?rss=1 Authors: Barbuti, P. A., Antony, P., Novak, G., Larsen, S. B., Berenguer-Escuder, C., Santos, B. F., Massart, F., Grossmann, D., Shiga, T., Ishikawa, K.-i., Akamatsu, W., Finkbeiner, S., Hattori, N., Krueger, R. Abstract: Parkinson's disease (PD) is characterized by the loss of A9 midbrain dopaminergic neurons and the accumulation of alpha-synuclein aggregates in remaining neurons. Many studies of the molecular and cellular basis of neurodegeneration in PD have made use of iPSC-derived neurons from patients with familial PD mutations. However, approximately half of the cells in the brain are glia, and their role facilitating neurodegeneration is unclear. We developed a novel serum-free protocol to generate midbrain astrocytes from patient-derived iPSCs harbouring the pathogenic p.A30P, p.A53T mutations in SNCA, as well as duplication and triplication of the SNCA locus. In our cellular model, aggregates of alpha-synuclein occurred only within the GFAP+ astrocytes carrying the pathogenic SNCA mutations. Assessment of spontaneous cytosolic calcium (Ca2+) release using Fluo4 revealed that SNCA mutant astrocytes released excess Ca2+ compared to controls. Unbiased evaluation of 3D mitochondrial morphometric parameters showed that these SNCA mutant astrocytes had increased mitochondrial fragmentation and decreased mitochondrial connectivity compared to controls, and reduced mitochondrial bioenergetic function. This comprehensive assessment of different pathogenic SNCA mutations derived from PD patients using the same cellular model enabled assessment of the mutation effect, showing that p.A53T and triplication astrocytes were the most severely affected. Together, our results indicate that astrocytes harbouring the familial PD mutations in SNCA are dysfunctional, suggesting a contributory role for dysfunctional astrocytes in the disease mechanism and pathogenesis of PD. Copy rights belong to original authors. Visit the link for more info
In this episodes... A VERY Brief History of Neuropsychology/The Only Seven People the MCAT Sees as Important to Neuropsychology The Organization of there Human Nervous System/The Autonomic (Sympathetic/Parasympathetic) Nervous System with Examples The Organization of the Brain/Meninges, Hindbrain, Midbrain, and Forebrain (more depth in next episode i.e. embryonic brain development). Song Used: Thank God by Sasha Sloan
This episode focuses on understanding the three main parts of your brain and I had to write this lesson and record this prior to the next podcast tomorrow with Dr. Friederike Fabritius as many of my questions to her will rely on the understanding of these three parts of the brain so I thought it was important to record this first. Let’s take a closer look at the human brain, so that the insights Dr. Fabritus will share tomorrow, will have more of an impact.The human brain is the most complex organ in the body. Parts of the brain communicate with each other and enable us to enjoy food, communicate, and feel emotions; the brain shapes our entire world and all of our experiences. Understanding how to harness the power that exists within your own body is the key to unlocking the code that controls your results and future. What this future looks like is up to you. Once you have an understanding of how your brain works, and you have some strategies to overcome the pitfalls associated with the three main parts of your brain, you can set yourself up for a razor’s edge advantage over someone else who might not be paying attention to the largest and most complex organ in the human body. To be honest, I was not paying attention to this part of the body until just a few years ago. No one had ever asked me what I was doing for my brain health—not until I started researching in the area of neuroscience did I know these strategies existed. So, don’t worry if this is new to you. We all start at this place.There are three parts of the brain that I think everyone should understand, whether you are five years old, or 55 years old, we can all understand the basics of how our brain operates for improved results.Understanding the Reptilian Brain: The Ancient Instinctual Brain also known as The Hindbrain The brain stem (imagine this part at the top of your spine on the back of your neck) is the oldest part of the brain and is often referred to as the reptilian brain.[i] This is where vital body functions such as heartbeat, respiration, body temperature, and digestion are all monitored and controlled. The brain stem also holds the reticular activating system (RAS), which is responsible for the brain’s alertness—regardless of whether we’re asleep or awake.This part of the brain functions to keep us alive and safe and works closely with the entire body as well as the limbic system to create our emotional state of mind. The brain stem does not work alone. It is linked to the limbic system above it (in the middle of the brain) to assist, for example, in creating both our fighting states when we feel anger and our fleeing states when we feel fear.[ii] This Ancient Instinctual Brain Controls Our-Sensory motor functions (how our body runs) Survival instinct of fight, flight, freeze, faint[iii]When we understand that we can't help the fact that when we feel fear with something, consciously or unconsciously, our Reptilian Brain reacts on its own with the urge to fight, flight, or freeze.FIGHT- is when we react instead of responding to a situation (those times when we let our emotions take control)FLIGHT- is when we run awayFREEZE- is when we stay frozen and don't even tryTo overcome the pitfalls of the Reptilian Brain, we just need to learn strategies for overcoming our fears that are natural, and instinctual, coming from the part of our brain that was designed to keep us alive. Those who are longtime meditators speak of the ability to take the time to respond to a situation rather than reacting but if you are looking for a quick fix, try these simple strategies.[iv]S-STOP whatever you are doingT-TAKE deep belly breaths to bring more oxygen to your brainO-OBSERVE and think “how am I feeling right now in the moment?” Can you name the emotion? When you can name the emotion, science has proven that soothing neurotransmitters are released to calm you down.[v]P- PROCEED with whatever you are doing with a new awareness. Our next guest Dr. Friederike Fabritius,[vi] talks about this strategy in her book, The Leading Brain: Neuroscience Hacks to Work Smarter, Better, Happier.[vii]She also dives into the importance of adding a sense of fun and fear to your work since fun will add the neurotransmitter dopamine that will help you to retain information better and boost your performance, while just the right amount of fear when you try new things, and push your boundaries will release noradrenaline, a positive hormone that’s released when you have a challenge. Adding fun and fear will prevent boredom and drive you towards focus where the brain will release acetyl choline during this time of focused attention to help us to achieve flow or these high levels of peak performance that we all seek.[viii]Understanding the Second Part of the Brain: The Limbic SystemAbove the brain stem and below the cerebellum (in the midbrain imagine this part of the brain in the middle) is a collection of structures about the size of a lemon, referred to as the limbic system and sometimes called the mammalian brain or Midbrain. Most of the structures in the limbic system are duplicated in each hemisphere. This area is also responsible for “regulating internal chemical order .”[ix] The Limbic Brain or The Emotional Brain Controls Our-Feelings/emotions Motivations The brain’s reward circuit Memory, and our Immune systemThis part of the brain responds really well with motivation and rewards and since it’s the seat of our emotions, this part of the brain will take over ALL the other parts of the brain because our emotional Limbic Brain always wins.[x]In this part of our brain we all have a REWARD and a THREAT system. Most of us work well when we can see the reward for what we are working on. Our brain will release dopamine as we check off our to-do list items and make progress towards our goals. When we are working in a reward state, we will be happy, in a good mood, high performing and achieving our goals. This state is where we should all aim to spend our time as we will be the most productive.But when we are in a threat system, our brain will release cortisol and our prefrontal cortex will shut down, making us unable to work as we go into the fight, flight, freeze state. Some people do work well with an element of threat to motivate them, (like when you have a deadline for something you are working on) but too much threat can cause too much stress and lead to eventual burn-out.[xi]To overcome the pitfalls of the Emotional Limbic System:Find ways to make the work you do fun so that dopamine (the neurotransmitter that helps us to feel pleasure and satisfaction) will be released and will help you to see rewards and will motivate you to move towards them.Laugh more because dopamine (this pleasure and satisfaction chemical) is released with laughter. Always keep that funny person on your team who makes everyone laugh. They will help boost the dopamine of your entire team, making everyone motivated towards their goals.Find ways to keep things new since the brain loves novelty. Remember—we don’t pay attention to boring things.[xii]Always push your boundaries and challenge yourself to prevent boredom. The brain will release the positive neurotransmitter noradrenaline that will increase alertness and energy. OTHER IMPORTANT PARTS OF THE LIMBIC SYSTEM that I think are important to know about.The thalamus is the first part of the brain to receive sensory information (except smell) coming from the outside world.The hippocampus plays a crucial role in converting short-term memory to long-term memory. The amygdala plays an important role with emotions, especially fear.The anterior cingulate connects attention, emotion, social function, and pain perception.[xiii]The Basal Ganglia is an important part of the brain connected to the cortex, thalamus and brainstem and is connected to procedural learning, habit learning, cognition and emotion. Stay tuned for the next episode to understand the power associated with this part of your brain.Finally, Understanding the Third Part of the Brain:The Neocortex/The Decision-Making Brain also called our Forebrain where our Prefrontal Cortex Lives.The neocortex is the “outer bark of the brain”[xiv] that consists of folded gray matter and resembles a walnut. (Imagine this part of the brain as being folded over the midbrain and connecting all parts together). It is divided into areas that control specific functions that “ultimately are about making maps of various things—from perceptions of the outside world to ideas about the brain and well-being .”[xv]The Genius, Decision-Making part of the brain is the newest part of the brain (think of it this way—the brain develops from back to front—the oldest part with our brain stem and the newest is the front of our brain) and it tells us to be LOGICAL and REASONABLE with everyone. This part of the brain controls ourThinking and reflecting Perceiving and remembering Reasoning and planning Language development Multiple intelligences, and our Awareness and self-awareness This is the part of our brain that determines the level of success we will see in our careers. It’s also the part of our brain that reacts when we are tired, or when someone pushes our buttons, we can lose control of the Decision-Making Brain and do or say things are not in our normal character.It is reassuring to know why we lose control, and how to repair our relationships with those around us when this occurs by addressing it, and stepping back, and then taking some time out before coming back to regain composure.To overcome the pitfalls of the Decision-Making Brain we can:Get plenty of sleep and exercise so that we keep our prefrontal cortex operating at its best.Remember that when we drink alcohol, it will interfere with our decision-making brain and too much alcohol can lead to poor judgment, and even impair your memory.[xvi]You can take brain supplements to help you to achieve more focus and alertness.[xvii] I follow Dr. Daniel Amen’s[xviii] work and have learned what my brain type is so that I can be sure to be taking the right supplements for my brain type[xix] and follow the best nutritional plan for brain health.When we can find strategies to keep our brain working at its best, we will perform at our best. I hope these strategies and an understanding of the 3 parts of your brain help you to achieve higher levels of achievement. I’m excited to speak with Dr. Friederike Fabritius tomorrow morning and will dive deeper into the neuroscience of leadership and high performance. See you next tomorrow.RESOURCES:Andrea Samadi Level Up: A Brain-Based Strategy to Skyrocket Student Success and Achievement (2015 Wheatmark, Tucson, AZ).(Lesson 2: Use Your Brain Wisely)REFERENCES[i] David D’Sousa, How the Brain Learns, 3rd Ed. Page 18 (Corwin Press, Thousand Oaks, CA, 2006).[ii] Dr . Daniel J . Siegel, “Brain Insights and Well-Being,” Inspire to Rewire, Psychology Today, January 7, 2015 https://www.psychologytoday.com/us/blog/inspire-rewire/201501/brain-insights-and-well-being[iii] ibid[iv] Friederike Fabritius, “Take Charge of our Emotions” Published Dec. 10, 2016 https://www.youtube.com/watch?v=liu3cbEB3H8&t=1759s[v] Dan Siegel “Name it to Tame it” YouTube Published Dec. 8th, 2014 https://www.youtube.com/watch?v=ZcDLzppD4Jc[vi]Friederike Fabritius: "Fun, Fear, and Focus: The Neurochemical Recipe for Achieving Peak Performance" | Talks at Google Published Jan.15, 2019 https://www.youtube.com/watch?v=pWi-oCySuFA[vii] The Leading Brain by Friederike Fabritius (TarcherPerigee; Reprint edition February 20, 2018). https://www.amazon.com/Leading-Brain-Neuroscience-Smarter-Happier/dp/0143129368/ref=sr_1_1?keywords=the+leading+brain&qid=1571680862&sr=8-1[viii] Friederike Fabritius: Dopamine, Acetylcholine, and Focused Attention https://www.youtube.com/watch?v=T0C93OcfzGk[ix] Dr . Joe Dispenza, “TedTalks with Dr . Joe Dispenza,” TED video, 17:50 posted February 8, 2013 https://www.youtube.com/watch?v=W81CHn4l4AM&t=105s[x] Friederike Fabritius “Why the Limbic System Always Wins” YouTube Published https://www.youtube.com/watch?v=bb5UITosUUI[xi] Friederike Fabritius Prefrontal Cortex, Limbic System and Performance YouTube PublishedOct. 26, 2016 https://www.youtube.com/watch?v=xDuQM94RT9M[xii] John Medina, Brain Rule #4 http://www.brainrules.net/attention[xiii] Dr . Daniel J . Siegel, “Brain Insights and Well-Being,” Inspire to Rewire, Psychology Today, January 7, 2015 https://www.psychologytoday.com/us/blog/inspire-rewire/201501/brain-insights-and-well-being[xiv] ibid[xv] ibid[xvi]Alcohol Memory Blackouts and the Brain https://pubs.niaaa.nih.gov/publications/arh27-2/186-196.htm[xvii]12 Prescriptions for Creating a Healthy Brain and Life by Dr. Daniel Amen Jan. 15, 2018 https://www.amenclinics.com/blog/12-prescriptions-for-creating-a-brain-healthy-life-part-1/[xviii] http://danielamenmd.com/[xix] https://brainhealthassessment.com/
Jeffrey S. Klein, MD, Editor of RadioGraphics, discusses six articles from the July-August 2019 issue of RadioGraphics. ARTICLES DISCUSSED: Mucinous Neoplasms of the Ovary: Radiologic-Pathologic Correlation., RadioGraphics 2019; 39:982–997.; Whole-Body Imaging of Multiple Myeloma: Diagnostic Criteria., RadioGraphics 2019; 39:1077–1097.; Midbrain, Pons and Medulla: Anatomy and Syndromes., RadioGraphics 2019; 39:1110–1125.; Congenital Oral masses: An Anatomic Approach to Diagnosis., RadioGraphics 2019; 39:1143–1160.; Skull Base-related Lesions at Routine Head CT from the Emergency Department: Pearls, Pitfalls, and Lessons Learned., RadioGraphics 2019; 39:1161–1182.; MR Imaging of Tumors and Tumor Mimics Within the Female Pelvis: Anatomic Pelvic Space-Based Approach., RadioGraphics 2019; 39:1205–1229.
Episode #5: Why won’t you just quit? For families, friends, and loved ones of those in addiction, this question is often asked. Therapist, Dennis Woodruff, helps answer this question by explaining the purpose of the midbrain and prefrontal cortex and how they are affected by addiction. The post Insane in the Midbrain appeared first on Love, Recovery, and Rock & Roll.
Children throughout India are being taught to see while blindfolded... apparently.
Brainstem Basics Your brainstem is the most basic area of the brain. The area of the brain that we have in common with almost all other levels of the animal kingdom. It extends right into the spinal cord. A lot of other whole body involuntary reflexes come from the spinal cord - that's another story for another day). 3 main parts Medulla oblongata - rhythm center (heart rate, breathing, swallowing, vomiting and coughing reflex) - they're all involuntary Pons (not ponds) - the bridge between the cerebellum hemispheres and other brain regions, helps coordinate the right side and left side of your body for complex activities Midbrain - sensory reflexes (also involuntary) - blinking, eye focusing, pupil dilation in response to light, visual and auditory startling reflex that kick-starts the "fight or flight cascade". Other eye focusing problems are not rooted in the midbrain. They are more likely rooted in the areas of the brain that control orbital muscles or in the areas that translate what your eyes are seeing, like a "lazy eye" or drifting eye or being cross-eyed. There are therapies that doctors prescribe to try and strengthen the weak eye. Blinking is usually a response to eye moisture. Connect with me Support us on Patreon *NEW* Join the Pharmacist Answers Podcast Community on Facebook Subscribe: iTunes, Stitcher, GooglePlay, TuneIn Radio Like the Facebook page Music Credits: “Radio Martini” Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0 http://creativecommons.org/licenses/by/3.0/
Caustic Regular Dr. Rob Tarzwell joins Joe, Toren, and Kevin in the premiere episode of our new series: "Caustic Anatomy Class", this episode focusing on the master control of it all: the brain! We'll talk about the history of brain knowledge, an introduction to the brain's structure, brain-eating amoebas, the "creepy threesome", several people walking and talking without a large part of their brain, brain tapeworms, and The Man With Two Brains and a skull-full of pop culture! Music: "Scatter Brain" by Frankie Masters And His Orchestra Links Caustic Anatomy Class Intro music from Creative Sound. Brain in a Jar trope Fungi from Yuggoth The Whisper in the Darkness Images Videos http://www.youtube.com/watch?v=jHxyP-nUhUY http://www.youtube.com/watch?v=nFY2PvkqB2M http://www.youtube.com/watch?v=zH6Cb8IYjOY http://www.youtube.com/watch?v=0xK-ulxa0m4 Anatomy of the Brain collated by Caustic researcher Cory The most common method used to divide the brain, is based on the three main regions that developed in the embryonic state: The Forebrain (or prosencephalon) the cerebrum (telencephalon) thalamus hypothalamus and pineal gland among other features (diencephalon, or interbrain). The Midbrain (or mesencephalon) located near the very center of the brain between the interbrain and the hindbrain, is composed of a portion of the brainstem. The Hindbrain (or rhombencephalon) Consists of the remaining brainstem (myelencephalon) as well as our cerebellum and pons (metencephalon). Brain cells can be broken into two groups: Neurons, or nerve cells, are the cells that perform all of the communication and processing within the brain. Neuroglia, or glial cells, act as the helper cells of the brain; they support and protect the neurons. In the brain there are four types of glial cells: Astrocytes which protect neurons by filtering nutrients out of the blood and preventing chemicals and pathogens from leaving the capillaries of the brain. They have also been observed to turn into neurons by virtue of the stem cell characteristic pluripotency. Oligodendrocytes wrap the axons of neurons in the brain to produce the insulation known as myelin. Microglia act much like white blood cells by attacking and destroying pathogens that invade the brain. Ependymal cells line the capillaries of the choroid plexuses and filter blood plasma to produce cerebrospinal fluid. The tissue of the brain can be broken down into two major classes: gray matter and white matter. Gray matter is made of mostly unmyelinated neurons, most of which are interneurons. The gray matter regions are the areas of nerve connections and processing. White matter is made of mostly myelinated neurons that connect the regions of gray matter to each other and to the rest of the body. Myelinated neurons transmit nerve signals much faster than unmyelinated axons do. You could imagine your brain's gray matter as suburbs and businesses, and the white matter as the express highway, carrying information to be processed. Parts of the Brain Cerebrum The cerebrum is the largest portion of the brain, and is responsible for most of the brain's function. It is divided into four sections: Frontal Lobe: Controls several elements including creative thought, problem solving, intellect, judgment, behavior, attention, abstract thinking, physical reactions, muscle movements, coordinated movements, smell and personality. Parietal Lobe: This lobe focuses on comprehension. Visual functions, language, reading, internal stimuli, tactile sensation and sensory comprehension are monitored here. Sensory Cortex - This receives information relayed from the spinal cord regarding the position of various body parts and how they are moving. This middle area of the brain can also be used to relay information from the sense of touch, including pain or pressure which is affecting different portions of the body. Motor Cortex- This helps the brain monitor and control movement ...
This lecture discusses the differentiation of the brain vesicles, including developmental distortions, the midbrain and the forebrain.
A neuroscientist manipulates a tiny brain region that controls avoidance behavior To support the show: www.patreon.com/carrytheone
Jim Barkovich from UCSF discusses a Review about midbrain and hindbrain disorders.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 03/06
Tue, 11 Nov 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/9515/ https://edoc.ub.uni-muenchen.de/9515/2/Borina_Frank.pdf Borina, Frank ddc:570, ddc:500, Fakultät für Biologi
This course covers the relation of structure and function at various levels of neuronal integration. Topics include functional neuroanatomy and neurophysiology, sensory and motor systems, centrally programmed behavior, sensory systems, sleep and dreaming, motivation and reward, emotional displays of various types, "higher functions" and the neocortex, and neural processes in learning and memory.
This course covers the relation of structure and function at various levels of neuronal integration. Topics include functional neuroanatomy and neurophysiology, sensory and motor systems, centrally programmed behavior, sensory systems, sleep and dreaming, motivation and reward, emotional displays of various types, "higher functions" and the neocortex, and neural processes in learning and memory.
Three dimensional eye rotations were measured using the magnetic search coil technique in a patient with a lesion of the right rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF) and in four control subjects. Up to 10° contralesional torsional deviations with each voluntary saccade were revealed, which also could be seen during bedside examination. There was no spontaneous nystagmus. Based on MRI criteria, the lesion involved the RIMLF but spared the interstitial nucleus of Cajal. To date, this deficit has not been described in patients. Our results support the hypothesis that the vertical--torsional saccade generator in humans is organised similarly as in monkeys: each RIMLF encodes torsional saccades in one direction, while both participate in vertical saccades.
Fri, 1 Jan 1988 12:00:00 +0100 http://epub.ub.uni-muenchen.de/3192/ http://epub.ub.uni-muenchen.de/3192/1/3192.pdf Schuller, Gerd; Radtke-Schuller, Susanne Schuller, Gerd und Radtke-Schuller, Susanne (1988): Midbrain areas as candidates for audio-vocal interface in echolocating bats. In: Nachtigall, P. E. (Hrsg.), Animal Sonar. Processes and performance. Plenum Press: New York u.a., pp. 93-98. Biol
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.22.047670v1?rss=1 Authors: Zhu, Z., Ma, Q., Yang, H., Miao, L., Pan, L., Li, K., Zhang, X., Wu, J., Hao, S., Lin, S., Ma, X., Hao, Y., Yu, Y.-q., Duan, S. Abstract: Animals display various aggressive behaviors essential for survival, while uncontrollable attacks and abnormal aggressive states have massive social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but whether there are circuits governing a general aggressive state to promote diverse aggressive behaviors remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to multiple aggression-provoking cues with graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice. Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors, but not mating. By encoding a general aggressive state, the pSI-PAG circuit universally drives multiple aggressive behaviors and thus may provide a potential target for alleviating human pathological aggression. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.21.053892v1?rss=1 Authors: Zweifel, L. S., Fellinger, L., Jo, Y. S., Hunker, A. C., Soden, M. E. Abstract: Discrimination between predictive and non-predictive threat stimuli decrease as threat intensity increases. The central mechanisms that mediate the transition from discriminatory to generalized threat responding remain poorly resolved. Here, we identify the stress- and dysphoria-associated kappa opioid receptor (KOR) and its ligand dynorphin (Dyn), acting in the ventral tegmental area (VTA), as a key substrate for regulating threat generalization. We identified several dynorphinergic inputs to the VTA and demonstrate that projections from the bed nucleus of the stria terminalis (BNST) and dorsal raphe nucleus (DRN) both contribute to anxiety-like behavior but differentially affect threat generalization. These data demonstrate that conditioned threat discrimination has an inverted -U- relationship with threat intensity and establish a role for KOR/Dyn signaling in the midbrain for promoting threat generalization. Copy rights belong to original authors. Visit the link for more info