Podcasts about Striatum

Ma chère cousine m'a prêté ce livre et il est teeellllllleeemment intéressant ! En gros ça parle de pourquoi notre cerveau ne nous aide vraiment pas à régler la crise climatique. Tout vient du Striatum qui a cinq buts: manger le plus possible, se reproduire, obtenir le plus d'informations, obtenir du pouvoir et le faire avec le minimum d'effort.Je lis des extraits, je commente certains mais pas tous. Je trouve ce libre vraiment super. Le Bug humain (sous-titré Pourquoi notre cerveau nous pousse à détruire la planète et comment l'en empêcher) est un essai de Sébastien Bohler, paru en 2019. Hébergé par Acast. Visitez acast.com/privacy pour plus d'informations.

ハーフマラソン参加を通じたコンディショニングの変化、Bluesky移行など。論文紹介は、valenceに応じた伝達物質放出の変化、生きた細胞からのトランスクリプトミクス、空腹による恐怖表象の変化 (12/15収録) Show Notes (番組HP): UW medのハーフマラソン 村上春樹のエッセイ 腸脛靭帯炎 ボストンマラソンのエントリー基準 Garminのスマートウォッチたち (割と山に特化したfenix 7を使ってます 萩) 萩原(暫定)おすすめデカフ1: Sightglass Coffee 萩原(暫定)おすすめデカフ2:Linea Coffee 宮脇おすすめKarma Coffee V60 手で押すタイプのエスプレッソマシン アーロンチェア Sayl Logitechの575 Mx Ergo S Logitech Lift エレコムのベアリングトラックボールマウス　日本では謎に高い NIH Armamentarium NatureでもBluesky移行の記事が出ていた Nikolas KaralisによるBluesky移行ガイド NeuroRadioのBlueskyアカウント American Football Cap'n Jazz このへんのバンドはより正確には”midwest emo”らしいです  Hiatus Kaiyote - Red Room Robert Glasperの生歌が下手すぎるRed Room Robert Glasper Experiment の Smells Like Teen Spirit Robert Glasper Trio - LIVE at The Village Vanguard Darkside Tyler, the Creator Kendrick LamarとSZA トム・ヨークのツアー 観光客に成り下がっている写真 The Smile 論文紹介パート 論文１：Encoding opposing valences through frequency-dependent transmitter switching in single peptidergic neurons Sung Han (気づいたらAssociate Profになってました) Richard Palmiter ポスドクにおける仕事 先に出たリソース論文の仕事 五十嵐さんが最初に出たとき Synapto pHluorine GabaとDopamineが一緒に放出されるケース Central Amygdalaはめちゃくちゃヘテロ Plateau Potential NNに出てた呼吸の論文 論文２：Live-cell transcriptomics with engineered virus-like particles Paul Blainey ピペットでちょっと吸うタイプのlive cell transcriptomics Exosomeを使ったケースについてのレビュー Gil Westmeyerラボから同じ時期に出た類似プレプリント CellNet CROP-seq Evan Macosko Synapse-seq Synaptosomeを分けてシーケンスするのではなくBarseqみたいな感じですね汗 最近出ていたTissueからの経時的intactサンプリング Jerzy Szablowski 論文３：Hunger modulates exploration through suppression of dopamine signaling in the tail of striatum Sabatiniラボ ケータイのラボからのプレプリント GRAB 今回使っているdLight3.8はRoshgadol et al., in preparationとのこと Robert Datta MoSeq Tail of Striatumのaversive stimulus coding Dattaがclosed loopでrewardingなdopamineを叩く この前のSaunders ポスドクのときにいたJanakラボ 似たタスクを作ったのは院生の頃っぽい RealTimeLinux Editorial Notes: ハーフ2時間は切れましたがベンチ100kg上がらなくなりました (萩原) このあと背中攣りました。そしてSteelcaseのThinkを拾いました (脇)

Toutes les astuces de Céline Brugioni, membre de la team My Positive Impact à retrouver chaque lundi sur Radio Monaco Feel Good. Hébergé par Ausha. Visitez ausha.co/politique-de-confidentialite pour plus d'informations.

In Part 2 of the Excitation and Inhibition phenomena, we discuss Metabolic "bank" account and demands of navigating the social world. We discuss if we have enough resources or if we will run a metabolic deficits (think burnout and avoidance, and social isolation). We cover NMDA and AMPA and different Autistic Phenotypes. In addition, we review Neuromodulators, which are vast in our biology and determine how and where to direct our attention and energy. Lastly, we discuss the medial Prefrontal Cortex and how it integrates the "self" with the outside world.Don't try to change an Autistic person because they are different than you or different than others. Don't let that offend your beliefs and capacity to apply critical thinking in life.https://www.nature.com/articles/s41398-023-02317-5https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723386/https://www.nature.com/articles/s41398-018-0155-1https://www.nature.com/articles/nature10360https://onlinelibrary.wiley.com/doi/full/10.1034/j.1601-183X.2003.00037.x?sid=nlm%3Apubmedhttps://www.nature.com/articles/s41380-022-01506-w(0:00) Introduction; Know Autism and Make Informed Decisions; Biological Aspects influencing Excitation / Inhibition Phenomena(4:30) Metabolic "Bank" Account and Resources; E/I creates criteria A and B; NMDA and AMPA, and more on the Striatum(10:02) Neuromodulators- Serotonin, Dopamine, Epinephrine and Norepinephrine, Acetylcholine; Active versus Passive Coping; Activating Systems and Cells and influencing Learning and Memory (Neuroplasticity); Nicotinic Receptors and Rapid-Excitation(15:20) medial Prefrontal Cortex (mPFC)- Metabolic demands and planning while considering Feelings, Integrating the Self and the Outside World; How E/I interacts; a brief explanation on Default Mode Network; Quieting the Body, or not; Information-Processing; Thalamocortical(20:19) Pursuits and Preference- Wanting and Having and being Autistic is fine, and others need to accept our phenotypes; sensory-input causes Faster Firing Rates in normal E/I- Image an imbalanced E/I(22:25) Wrap-up and understanding Autism, and Contact Info

Le striatum, le chef d'orchestre méconnu de nos décisions

aux éditions Bouquins. Entretien avec Sylvie Hazebroucq. Rentrée Sciences-Humaines automne 2023.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.24.550364v1?rss=1 Authors: Bender, B. N., Stringfield, S. J., Torregrossa, M. M. Abstract: A preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking when drug seeking is goal-directed but not habitual. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habitual cue-induced cocaine seeking and how it is impacted by cue extinction. Rats trained to self-administer cocaine paired with an audiovisual cue on schedules of reinforcement that promote goal-directed or habitual cocaine seeking had different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium and dopamine responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habitual behavior and the DLS are unaffected. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.05.04.539488v1?rss=1 Authors: Gayden, J., Puig, S., Srinivasan, C., Buck, S. A., Gamble, M. C., Glausier, J. R., Tejeda, H. A., Dong, Y., Pfenning, A. R., Logan, R., Freyberg, Z. Abstract: Striatal dopamine (DA) neurotransmission is critical for an array of reward-related behaviors and goal-directed motor control. In rodents, 95% of striatal neurons are GABAergic medium spiny neurons (MSNs) that have been traditionally segregated into two subpopulations based on the expression of stimulatory DA D1-like receptors versus inhibitory D2-like receptors. However, emerging evidence suggests that striatal cell composition is anatomically and functionally more heterogenous than previously appreciated. The presence of MSNs that co-express multiple DA receptors offers a means to more accurately understand this heterogeneity. To dissect the precise nature of MSN heterogeneity, here we used multiplex RNAscope to identify expression of three predominantly expressed DA receptors in the striatum: DA D1 (D1R), D2 (D2R), and D3 (D3R) receptors. We report heterogenous subpopulations of MSNs that are distinctly distributed across the dorsal-ventral and rostral-caudal axes of the adult mouse striatum. These subpopulations include MSNs that co-express D1R and D2R (D1/2R), D1R and D3R (D1/3R), and D2R and D3R (D2/3R). Overall, our characterization of distinct MSN subpopulations informs our understanding of region-specific striatal cell heterogeneity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.26.538415v1?rss=1 Authors: Kato, T., Tanaka, K. F., Natsubori, A. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.13.536699v1?rss=1 Authors: Falck, J., Zhang, L., Raffington, L., Mohn, J. J., Triesch, J., Heim, C., Shing, Y. L. Abstract: The hippocampal-dependent memory system and striatal-dependent memory system modulate reinforcement learning depending on feedback timing in adults, but their contributions during development remain unclear. In a 2-year longitudinal study, 6-to-7-year-old children performed a reinforcement learning task in which they received feedback immediately or with a short delay following their response. Learning in children was found to be sensitive to feedback timing modulations in their reaction time and inverse temperature parameter, which quantifies value-guided decision-making. They showed longitudinal improvements towards more optimal value-based learning, and their hippocampal volume showed protracted maturation. Better delayed model-derived learning covaried with larger hippocampal volume longitudinally, in line with the adult literature. In contrast, a larger striatal volume in children was associated with both better immediate and delayed model-derived learning longitudinally. These findings show, for the first time, an early hippocampal contribution to the dynamic development of reinforcement learning in middle childhood, with neurally less differentiated and more cooperative memory systems than in adults. 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/2023.03.22.533839v1?rss=1 Authors: Garma, L., Harder, L., Barba-Reyes, J. M., Diez-Salguero, M., Serrano-Pozo, A., Hyman, B. T., Munoz-Manchado, A. B. Abstract: Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed single-nucleus RNA-sequencing (snRNA-seq) of postmortem human caudate nucleus (CN) and putamen (Pu) samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes. We provide specific markers for all subclasses and validated some of them with quantitative in situ fluorescence hybridization, such as a novel PTHLH-expressing population that exhibits different abundance and gene expression between CN and Pu. For the most abundant interneuron populations in human striatum, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate our dataset with several prior smaller human striatal snRNA-seq studies, thus supporting the generalizability of this new harmonized taxonomy. 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/2023.03.06.531405v1?rss=1 Authors: Sanabria, B. D., Baskar, S. S., Yonk, A. J., Lee, C. R., Margolis, D. J. Abstract: The anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and is considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in the strength of their connections with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert an opposing influence on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that SPNs are less innervated by S1 compared to M1, but FSIs receive a similar number of inputs from both M1 and S1. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPNs and FSIs. Notably, clusters of inputs were prevalent in SPNs but not FSIs. Our results suggest that SPNs have stronger functional connectivity to M1 compared to S1 due to a higher density of synaptic inputs. The clustering of M1 and S1 inputs onto SPNs but not FSIs suggest that cortical inputs are integrated through cell-type specific mechanisms and more generally have implications for how sensorimotor integration is performed in the striatum. 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/2023.03.05.531219v1?rss=1 Authors: Yun, M., Masafumi, N., Kawai, T., Kunimatsu, J., Yamada, H., Kim, H., Matsumoto, M. Abstract: Individuals often assess past decisions by comparing what was gained with what would have been gained had they acted differently. Thoughts of past alternatives that counter what actually happened are called counterfactuals . Recent theories emphasize the role of the prefrontal cortex in processing counterfactual outcomes in decision-making, although how subcortical regions contribute to this process remains to be elucidated. Here we report a clear distinction among the roles of the orbitofrontal cortex, ventral striatum and midbrain dopamine neurons in processing counterfactual outcomes in monkeys. Our findings suggest that actually-gained and counterfactual outcome signals are both processed in the cortico-subcortical network constituted by these regions but in distinct manners, and integrated only in the orbitofrontal cortex in a way to compare these outcomes. This study extends the prefrontal theory of counterfactual thinking and provides key insights regarding how the prefrontal cortex cooperates with subcortical regions to make decisions using counterfactual information. 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/2023.03.01.530671v1?rss=1 Authors: Kasanga, E., Han, Y., Navarrete, W., McManus, R., Shifflet, M., Parry, C., Barahona, A., Manfredsson, F., Nejtek, V., Richardson, J. R., Salvatore, M. F. Abstract: Although glial cell line-derived neurotrophic factor (GDNF) showed efficacy in preclinical and early clinical studies to alleviate parkinsonian signs in Parkinsons disease (PD), later trials did not meet primary endpoints, giving pause to consider further investigation. While GDNF dose and delivery methods may have contributed to diminished efficacy, one crucial aspect of these clinical studies is that GDNF treatment across all studies began ~8 years after PD diagnosis; a time point representing several years after near 100% depletion of nigrostriatal dopamine markers in striatum and at least 50% in substantia nigra (SN), and is later than the timing of GDNF treatment in preclinical studies. With nigrostriatal terminal loss exceeding 70% at PD diagnosis, we utilized hemi-parkinsonian rats to determine if expression of GDNF family receptor, GFR-alpha1, and receptor tyrosine kinase, RET, differed between striatum and SN at 1 and 4 weeks following a 6-hydroxydopamine (6-OHDA) lesion. Whereas GDNF expression changed minimally, GFR-alpha1 expression decreased progressively in striatum and in tyrosine hydroxylase positive (TH+) cells in SN, correlating with reduced TH cell number. However, in nigral astrocytes, GFR-alpha1 expression increased. RET expression decreased maximally in striatum by 1 week, whereas in the SN, a transient bilateral increase occurred that returned to control levels by 4 weeks. Expression of brain-derived neurotrophic factor (BDNF) or its receptor, TrkB, were unchanged throughout lesion progression. Together, these results reveal that differential GFR-alpha1 and RET expression between the striatum and SN, and cell-specific differences in GFR-alpha1 expression in SN, occur during nigrostriatal neuron loss. Targeting loss of GDNF receptors appears critical to enhance GDNF therapeutic efficacy against nigrostriatal neuron loss. 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/2023.02.20.529283v1?rss=1 Authors: Cerri, D. H., Albaugh, D. L., Walton, L. R., Katz, B., Wang, T.-W., Chao, T.-H. H., Zhang, W., Nonneman, R. J., Jiang, J., Lee, S.-H., Etkin, A., Hall, C. N., Stuber, G. D., Shih, Y.-Y. I. Abstract: The striatum is the primary input nucleus of the basal ganglia, widely studied for its complex roles in health and disease. Functional magnetic resonance imaging (fMRI) studies are essential for discerning striatal function, however the relationship between neuronal and hemodynamic activity, critical for interpreting fMRI signals, has not been rigorously examined in striatum. We find that optogenetic stimulation of striatal neurons or afferents evokes negative striatal fMRI responses in rats that can occur despite broad increases in local neuronal activity. Intra-striatal pharmacological manipulations suggest that opioidergic, but not dopaminergic transmission contributes to negative striatal fMRI signals (the latter instead associated with positive signals). Striatal neuronal activity peaks are also associated with negative hemodynamic signals in behaving rats. Negative fMRI responses are observed in human striatum under conditions of anticipated neuronal activity increases. Our results prompt consideration of local cellular and neurochemical environments along with neuronal activity in fMRI signal interpretation. 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/2023.01.03.522560v1?rss=1 Authors: Lousada, E., Kliesmete, Z., Janjic, A., Burguiere, E., Enard, W., Schreiweis, C. Abstract: During cortico-basal ganglia dependent learning, relevant environmental information is associated with certain outcomes; such learning is essential to generate adaptive behaviour in a continuously changing environment. Through repetitive trial-and-error experiences, actions are optimized and cognitive associative load can be relieved through consolidation and automatization. Although the molecular basis of learning is well studied, region-specific genome-wide expression profiles of the striatum, the major input region of cortico-basal ganglia circuits, during learning are lacking. Here we combined an automated operant conditioning paradigm with an efficient RNA-sequencing protocol to compare expression profiles among three learning stages in three striatal regions per hemisphere in a total of 240 striatal biopsies. Notably, the inclusion of matched yoked controls allowed reliably identifying learning-related expression changes. With 593 differently expressed genes (3.3% of all detected genes), we find the strongest effect of learning at an early, goal-directed stage across all three striatal region and identify a total of 921 learning-related expression changes. Our dataset provides a unique resource to study molecular markers of striatal 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/2022.11.30.518587v1?rss=1 Authors: Waernberg, E., Kumar, A. Abstract: It is well established that midbrain dopaminergic neurons support reinforcement learning (RL) in the basal ganglia by transmitting a reward prediction error (RPE) to the striatum. In particular, different computational models and experiments have shown that a striatum-wide RPE signal can support RL over a small discrete set of actions (e.g. no/no-go, choose left/right). However, there is accumulating evidence that the basal ganglia functions not as a selector between predefined actions, but rather as a dynamical system with graded, continuous outputs. To reconcile this view with RL, there is a need to explain how dopamine could support learning of dynamic outputs, rather than discrete action values. Inspired by the recent observations that besides RPE, the firing rates of midbrain dopaminergic neurons correlate with motor and cognitive variables, we propose a model in which dopamine signal in the striatum carries a vector-valued error feedback signal (a loss gradient) instead of a homogeneous scalar error (a loss). Using a recurrent network model of the basal ganglia, we show that such a vector-valued feedback signal results in an increased capacity to learn a multidimensional series of real-valued outputs. The corticostriatal plasticity rule we employed is based on Random Feedback Learning Online learning and is a fully local, 'three-factor' product of the presynaptic firing rate, a post-synaptic factor and the unique dopamine concentration perceived by each striatal neuron. Crucially, we demonstrate that under this plasticity rule, the improvement in learning does not require precise nigrostriatal synapses, but is compatible with random placement of varicosities and diffuse volume transmission of dopamine. 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/2022.11.08.515650v1?rss=1 Authors: Espinosa, P., Girard, B., Lucchini, M., Campanelli, F., Tiriticco, V., Bellone, C. Abstract: The decision to approach or avoid a conspecific is fundamental for survival. Affiliative (prosocial) interactions favor approach behaviors, while antagonistic (aggressive) contacts trigger avoidance. Here we ask how the brain encodes the valence of social interaction. We focused on the nucleus accumbens (NAc), a brain region implicated in social reward processing. We observed that social interactions activate D1-expressing medium spiny neurons (D1-MSNs) regardless of their valence. However, afferent D1- expressing neurons of the anterior insular cortex (AIC) exhibited distinct activity patterns coding for prosocial and aggressive social interaction, respectively. As a result, distinct forms of synaptic plasticity were elicited at the AIC to NAc synapses. Thus, the valence of social interaction induces distinct neural activity in the AIC, which teaches the animal to approach and avoid conspecifics in the future. 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/2022.11.07.515477v1?rss=1 Authors: Vassiliadis, P., Beanato, E., Popa, T., Windel, F., Morishita, T., Neufeld, E., Duque, J., Derosiere, G., Wessel, M. J., Hummel, F. C. Abstract: Reinforcement feedback can improve motor learning, but the underlying brain mechanisms remain unexplored. Especially, the causal contribution of specific patterns of oscillatory activity within the human striatum is unknown. To address this question, we exploited an innovative, non-invasive deep brain stimulation technique called transcranial temporal interference stimulation (tTIS) during reinforcement motor learning with concurrent neuroimaging, in a randomised, sham-controlled, double-blind study. Striatal tTIS applied at 80Hz, but not at 20Hz, abolished the benefits of reinforcement on motor learning. This effect was related to a selective modulation of neural activity within the striatum. Moreover, 80Hz, but not 20Hz, tTIS increased the neuromodulatory influence of the striatum on frontal areas involved in reinforcement motor learning. These results show for the first time that tTIS can non-invasively and selectively modulate a striatal mechanism involved in reinforcement learning, opening new horizons for the study of causal relationships between deep brain structures and human behaviour. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.01.514407v1?rss=1 Authors: Singer, N., Poker, G., Dunsky, N., Nemni, S., Doron, M., Baker, T., Dagher, A., Zatorre, R., Hendler, T. Abstract: Reward processing is essential for our mental-health and well-being. Here, we present the development and validation of a scalable fMRI-informed EEG model related to reward processing in the ventral-striatum (VS); a central reward circuit node. Simultaneous EEG/fMRI data were acquired from 17 healthy individuals listening to pleasurable music, and used to construct a one-class regression model for predicting the reward-related VS-BOLD signal using spectro-temporal features from the EEG. Validation analyses, applied on EEG/fMRI data from a different group (N=14), revealed that the EEG model predicted VS-BOLD activation from the simultaneous EEG to a greater extent than a model derived from another anatomical region. The VS-EEG-model was also modulated by musical pleasure and predictive of the VS-BOLD during a monetary reward task, further indicating it functional relevance. These findings provide compelling evidence for the use of a scalable yet precise EEG-only probe of VS-originated reward processing, which could serve for process specific neruo-monitoring and -modulation. 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/2022.10.28.514217v1?rss=1 Authors: Tomar, M., Rodger, J., Moretti, J. Abstract: Overreliance on habit is linked with disorders such as drug addiction and obsessive-compulsive disorder and there is increasing interest in the use of repetitive transcranial magnetic stimulation (rTMS) to alter neuronal activity in the relevant pathways and reduce relapse or accelerated shift towards habit formation. Here we studied the brains of ephrin-A2A5-/- mice, which previously showed perseverative behaviour in progressive-ratio tasks, associated with low cellular activity in nucleus accumbens. We investigated if rTMS treatment had altered the hierarchical recruitment of brain regions from ventral to dorsal striatum associated with abnormal habit formation in these mice. Brain sections of mice that underwent progressive-ratio tasks with and without LI-rTMS were taken from a previous study. Striatal regions were stained for neuronal activation with c-Fos and for medium spiny neurons with DARPP32. Qualitative analysis was carried out for other neuronal subtypes in the striatum - GABAergic, parvalbumin-expressing and cholinergic interneurons. Contrary to our hypothesis, we found neuronal activity in ephrin-A2A5-/- mice still reflected goal-directed behaviour. However, we saw that the dorsolateral striatum contributed more to total striatal activity in untreated ephrin-A2/A5-/- mice. This supported our hypothesis that ephrin-A2/A5-/- mice have greater c-Fos activity in habit-associated striatal regions. LI-rTMS in ephrin-A2A5-/- mice also appeared to delay the shift from goal-directed to habitual behaviour as suggested by increased activation in dorsomedial striatum and nucleus accumbens. 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/2022.10.07.511354v1?rss=1 Authors: Martel, A.-C., Apicella, P. Abstract: The striatum and its dopaminergic input participate in temporal processing and numerous studies provide evidence that interactions between dopamine and acetylcholine are critical for striatal functioning. However, the role of local cholinergic innervation of the striatum in behaviors requiring precise timing has not been specifically investigated. Here, we recorded from presumed striatal cholinergic interneurons, identified as tonically active neurons (TANs), in two male rhesus monkeys performing self-initiated movements after specified learned time intervals have elapsed since a visual cue. We found that 38% of all recorded TANs responded to the cue with a pause in firing and the strength of these responses could be modulated according to the duration of the interval being timed and the accuracy of time estimates. By examining the TAN response to the reward itself and by recording from TANs during a Pavlovian procedure in which no action was required, we found evidence that TAN activity modulation may potentially reflect differences in the animal's prediction of reward. Thus, besides their well-known role in predicting and detecting rewarding events, TANs may generate signals related to the processing of time. Our findings suggest a role of the local cholinergic circuitry in the representation of time within the striatum. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.06.511163v1?rss=1 Authors: Alves, A. C. d. B., Speck, A. E., Farias, H. R., dos Santos, N. S., Pannata, G. d. S., Tavares, A. P., Martins, L. M., de Oliveira, J., Tome, A. R., Cunha, R., Aguiar, A. S. Abstract: Caffeine is one of the main ergogenic resources used in exercise and sports. Previously, we presented the ergogenic mechanism of caffeine through neuronal A2AR antagonism in the central nervous system [1]. We demonstrate here that the striatum rules the ergogenic effects of caffeine through neuroplasticity changes. Thirty-four Swiss (8-10 weeks, 47 {+/-} 1.5 g) and twenty-four C57BL6 (8-10 weeks, 23.9 {+/-} 0.4 g) adult male mice were challenged in behavior and electrophysiology experiments using caffeine and SH-SY5Y cells for energetic metabolism. Systemic (15 mg/kg, i.p.) or striatal (bilateral, 15 g) caffeine was psychostimulant in the open field (p less than 0.05) and increased gripping muscle power (p less than 0.05). Caffeine also induced long-term potentiation (LTP) in striatal slices (p less than 0.05) and increased mitochondrial mass (p less than 0.05) and membrane potential p less than 0.05) in SH-SY5Y dopaminergic cells. In summary, our results demonstrate that caffeine stimulation in the striatum produces ergogenic effects accompanied by an LTP, possibly associated with acute increased mitochondrial metabolism observed in dopaminergic cell lines. 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/2022.09.27.509680v1?rss=1 Authors: Giuliano, C., Marti-Prats, L., Domi, A., Puaud, M., Pena-Oliver, Y., McKenzie, C., Everitt, B. J., Belin, D. Abstract: Humans greatly differ in how they cope with stress, a natural behaviour learnt through negative reinforcement. Some individuals engage in displacement activities, others in exercise or comfort eating, and others still in alcohol use. Across species, adjunctive behaviors, such as polydipsic drinking, are used as a form of displacement activity that reduce distress. Some individuals, in particular those that use alcohol to self-medicate, tend to lose control over such coping behaviors, which become excessive and compulsive. However, the psychological and neural mechanisms underlying this individual vulnerability have not been elucidated. Here we tested the hypothesis that the development of compulsive adjunctive behaviors stems from the functional engagement of the dorsolateral striatum (DLS) dopamine-dependent habit system after a prolonged history of adjunctive responding. We measured in longitudinal studies in male Sprague Dawley rats the sensitivity of early established vs compulsive polydipsic water or alcohol drinking to a bilateral infusion of the dopamine receptor antagonist -flupentixol into the anterior DLS (aDLS). While most rats acquired a polydipsic drinking response with water, others only did so with alcohol. Whether reliant on water or alcohol, the acquisition of this coping response was insensitive to aDLS dopamine receptor blockade. In contrast, after prolonged experience, adjunctive drinking became dependent on the aDLS dopamine-dependent habit system at a time it was compulsive in vulnerable individuals. These data suggest that habits may develop out of negative reinforcement and that the engagement of their underlying striatal system is necessary for the manifestation of adjunctive behaviors. 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/2022.09.16.507381v1?rss=1 Authors: Khoo, S. Y.-S., Samaha, A.-N. Abstract: After a history of intermittent cocaine intake, rats develop patterns of drug use characteristic of addiction. The dorsal striatum is involved in the increased pursuit of cocaine after intermittent drug self-administration experience. Within the dorsal striatum, chronic cocaine use changes metabotropic glutamate type II receptor (mGlu2/3) density and function. We examined the extent to which activity at these receptors mediates responding for cocaine after intermittent cocaine use. In Experiment 1, male Wistar rats (n = 11) self-administered 0.25 mg/kg/infusion cocaine during 10 daily intermittent access (IntA) sessions (5 min ON/25 min OFF, for 5 h/session). We then examined the effects of intra-dorsal striatum infusions of the mGlu2/3 receptor agonist LY379268 (0, 1, and 3 g/hemisphere) on cocaine self-administration under a progressive ratio schedule of reinforcement. We observed a non-significant tendency for LY379268 to reduce responding for cocaine. In Experiment 2, we used a larger sample of male (n = 11) and female (n = 10) rats. Across 10 IntA sessions, the sexes showed similar levels of cocaine intake. Across the sexes, locomotion significantly increased over sessions, suggesting that rats developed psychomotor sensitization to self-administered cocaine. After 10 IntA sessions, intra-dorsal striatum LY379268 significantly reduced breakpoints achieved for cocaine, active lever presses, and cocaine infusions earned under progressive ratio. LY379268 had no effects on locomotion or inactive lever presses, indicating no motor effects. These results suggest that mGlu2/3 receptor activation in the dorsal striatum suppresses incentive motivation for cocaine, and this holds promise for anti-addiction therapeutics. 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/2022.09.09.507300v1?rss=1 Authors: Krok, A. C., Mistry, P., Li, Y., Tritsch, N. X. Abstract: External rewards like food and money are potent modifiers of behavior. Pioneering studies established that these salient sensory stimuli briefly interrupt the tonic cell-autonomous discharge of neurons that produce the neuromodulators dopamine (DA) and acetylcholine (ACh): midbrain DA neurons (DANs) fire a burst of action potentials that broadly elevates DA levels in striatum at the same time as striatal cholinergic interneurons (CINs) produce a characteristic pause in firing. These phasic responses are thought to create unique, temporally-limited conditions that motivate action and promote learning. However, the dynamics of DA and ACh outside explicitly-rewarded situations remain poorly understood. Here we show that extracellular levels of DA and ACh fluctuate spontaneously in the striatum of mice and maintain the same temporal relationship as that evoked by reward. We show that this neuromodulatory coordination does not arise from direct interactions between DA and ACh within striatum. Periodic fluctuations in ACh are instead controlled by glutamatergic afferents, which act to locally synchronize spiking of striatal cholinergic interneurons. Together, our findings reveal that striatal neuromodulatory dynamics are autonomously organized by distributed extra-striatal afferents across behavioral contexts. The dominance of intrinsic reward-like rhythms in DA and ACh offers novel insights for explaining how reward-associated neural dynamics emerge and how the brain motivates action and promotes learning from within. 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/2022.08.31.505994v1?rss=1 Authors: Kershberg, L., Banerjee, A., Kaeser, P. S. Abstract: Mechanisms of neuromodulatory transmission in the brain remain ambiguous. Dopamine is a prototypical neuromodulator, and it was recently found that its secretion relies on active zone-like release site assemblies. Here, we use in vivo biotin-identification (iBioID) proximity proteomics in mouse striatum to isolate dopamine release site proteins enriched over the general dopamine axonal protein content. Using three bait proteins, we identified 527 proteins that fall into several synaptic protein classes, including active zone, calcium regulatory and synaptic vesicle proteins. We also detected many proteins not previously associated with synaptic exocytosis. Knockout of the presynaptic organizer protein RIM profoundly disrupted dopamine release site composition assessed by iBioID, while Synaptotagmin-1 knockout did not. Alpha-synuclein, a protein linked to Parkinson's disease, was enriched at release sites, and this enrichment was lost in both tested mutants. We conclude that RIM organizes scaffolded dopamine release sites and we define the protein composition of these sites. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer

TWiN reviews how, in a mouse stroke model, recovery of movement is associated with the remaining cortex and the striatum coordinating their activity together. Hosts: Ori Lieberman, Timothy Cheung, and Vivianne Morrison Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Recovery after stroke in mice (Cell Rep) Timestamps by Jolene. Thanks! Music is by Ronald Jenkees Send your neuroscience questions and comments to twin@microbe.tv

I read from corpus delicti to correct.     The word of the episode is "corpus striatum". https://en.wikipedia.org/wiki/Striatum     "The Dictionary - Letter A" on YouTube   "The Dictionary - Letter B" on YouTube   "The Dictionary - Letter C" on YouTube     Featured in a Top 10 Dictionary Podcasts list! https://blog.feedspot.com/dictionary_podcasts/     Backwards Talking on YouTube: https://www.youtube.com/playlist?list=PLmIujMwEDbgZUexyR90jaTEEVmAYcCzuq     dictionarypod@gmail.com https://www.facebook.com/thedictionarypod/ https://twitter.com/dictionarypod https://www.instagram.com/dictionarypod/ https://www.patreon.com/spejampar 917-727-5757

Was ist Sucht? Welche Kriterien musst du erfüllen, um dich als abhängig zu qualifizieren? Was ist ein Suchtgedächtnis, und kann man es löschen? Können ehemals Abhängige irgendwann wieder kontrolliert trinken? Wie kann man Rückfällen vorbeugen? Mit diesen und vielen anderen hochinteressanten Fragen löchern wir in dieser Folge Dr. Miriam Sebold, die an der Berliner Charité zu Alkoholabhängigkeit forscht. Miriam nimmt uns mit auf einen Ausflug in das süchtige Hirn. Wir besuchen unseren inneren Erwachsenen im präfrontalen Kortex, surfen auf den soliden Furchen unserer Großhirnrinde und erfahren, wie wir unser Striatum trainieren können, um gegen alle Verführungen gewappnet zu sein.Dr. Miriam Sebold ist Diplom Psychologin und erforscht Lernprozesse und Entscheidungsverhalten bei Substanzabhängigkeit, insbesondere bei Alkoholabhängigkeit. Ihre Forschungsarbeit beschäftigt sich besonders mit der Frage, welche Faktoren zum Rückfall der Patient:innen führen, ob es im Gehirn Indikatoren dafür gibt, wer besonders Rückfall-gefährdet ist und welche Therapien man entwickeln kann, um Abhängigen besser zu helfen. In diesem Zusammenhang hat uns Miriam auch noch auf eine laufende Studie hingewiesen, für die immer wieder Proband:innen gesucht werden. Die Studie findet in Berlin, Mannheim und Dresden statt. Sie untersucht die Trinkgewohnheiten von Personen, die ihr eigenes Trinken als problematisch wahrnehmen. Wenn ihr mitmacht, könnt ihr der Wissenschaft dabei helfen, Abhängigkeit besser zu verstehen und bessere Therapien zu entwickeln. Die ReCoDe Studie findet ihr hier oder einfach, wenn ihr »Recode Studie« googelt. See acast.com/privacy for privacy and opt-out information.

Notre cerveau, bien malin, identifie les comportements qui apportent une récompense et il en veut toujours plus ! Qu'est-ce qu'il le pousse à agir ainsi ? Pourquoi nos comportements deviennent-ils parfois compulsifs ? Comment reprendre la télécommande, tempérer et mettre du sens dans nos actes ? À vous d'écouter pour connaître ces clés ! ******** Retrouvez le texte de l'épisode sur notre blog. En vous abonnant sur Itunes pour recevoir les notifications et en nous laissant un avis, vous nous envoyez des bulles de bonheur ! En suivant notre actu sur FB @2minutesdebonheur et sur insta @2minutesdebonheur, vous profiterez gratuitement de pleins de trucs, d'astuces et de mises en pratique liés au podcast de la semaine. Inscrivez-vous à la newsletter, vous serez ainsi notifié de nos nouveaux épisodes et vous recevrez en cadeau 2 cartes de jeux 2 minutes inédites par mois. Et surtout, partagez nos épisodes à tous ceux qui veulent prendre le temps d'être heureux ! *********** Notre blog Notre podcast sur Itunes Nos pages Facebook et Instagram Inscription à la newsletter

Pour ce premier épisode, Anna et Julien discutent du « bug humain » de Sébastien Bohler et des nombreuses questions qu'il soulève !  Sebastien Bohler, journaliste et neurobiologiste, analyse astucieusement sous le prisme du striatum* nos comportements de surconsommation. En effet, cette partie du cerveau, historiquement câblée pour adopter 5 comportements de survie est identifiée aujourd'hui au coeur du circuit de la récompense et de l'addiction.  Anna parcourera dans cette chronique ces 5 comportements vitaux mais aussi deux expériences de référence en neurosciences cognitives. La première réalisée en 1954 a permis de découvrir fortuitement ce fameux striatum. La deuxième datant de 1972 illustre le bras de fer qui se tient entre le striatum et le neocortex, et sera reprise dans les travaux du Prix Nobel Daniel Kahnemann "Thinking Fast & Slow". *Références pour aller plus loin  Le striatum est parfois appelé cerveau reptilien, mais ce terme reflète une origine du développement cérébral parfois controversé chez les scientifiques.   Le Bug humain, Éditions Robert Laffont, 2019 (ISBN 978-2-221-24010-6) Olds J, Milner P (1954). "Positive reinforcement produced by electrical stimulation of septal area and other regions of rat brain". Journal of Comparative and Physiological Psychology. 47 (6): 419–27. doi:10.1037/h0058775. PMID 13233369.   Daniel Kahneman (October 25, 2011). Thinking, Fast and Slow. Macmillan. ISBN 978-1-4299-6935-2. Retrieved April 8, 2012

Vi älskar dom som älskar oss  Det är viktigt att komma ihåg att förälskelse är just "för - älskelse" och inte kärlek. Det är en tid där vi "badar" i hormoner som får oss att känna oss härliga och livslevande. Vi vill vara nära och all vår uppmärksamhet går till den som triggar vår lust....  en kort stund. Den del av hjärnan som styr oss mot belöningar är striatum, hjärnans belöningsstruktur. Striatum aktiveras av sådant vi gillar - och det gäller allt från trevliga människor till smaskiga chokladkakor och uppskattande blickar. När belöningssystemet är aktiverat ge den hjärnan en härlig dusch och vi känner oss nöjda. Denna signal uppmuntrar oss att fortsätta att upprepa det beteendet som gav oss den behagliga känslan - om och om igen.   Som du vet är vi gjorda för kontakt. Det gör bland annat förälskelsen till en sockersöt bakelse. Som du förstår dras vi även till massor av saker som ger hjärnan en kortsiktig upplevelse av belöning. Tyvärr leder ofta kortsiktiga stimuli till långsiktig tokighet. Här springer vi helt enkelt från oss själva.  Förälskelsen ska - och kommer att gå över. Med det i åtanke ska vi se vårt grundbehov; Alla behöver vi bli sedda med varma och uppskattande ögon. Vi älskar dom som älskar oss och vi gillar dom som ser, hör och förstår oss.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.19.390286v1?rss=1 Authors: Chiuffa Tunes, G., de Oliveira, E. F., Vieira, E. U. P., Caetano, M. S., Cravo, A. M., Reyes, M. B. Abstract: Although time is a fundamental dimension of life, we do not know how the brain encodes the temporal information. Several brain areas underlie the temporal information, such as the hippocampus, prefrontal cortex, and striatum, but evidence of how they cooperate to process temporal information is scarce. Notably, the analysis of neural activity during learning are rare, mainly because timing tasks usually take a long time to train. Here we investigated how the time encoding evolves when animals learn to time a 1.5 s interval. We designed a novel training protocol where rats go from naive- to proficient-level timing performance within a single session, allowing us to investigate neuronal activity from very early learning stages. We used pharmacological experiments and machine-learning algorithms to evaluate the level of time encoding in the medial prefrontal cortex and the dorsal striatum. Our results show a double dissociation between the roles of the medial prefrontal cortex and the dorsal striatum during temporal learning, where the former commits to early learning stages while the latter become more engaged as animals become more proficient in the task. Copy rights belong to original authors. Visit the link for more info

As people age they can often be affected by 'motivation decline', that is the loss of motivation to learn new things or even engage in everyday activities.  Professor John Reynolds, a neuroscientist from the University of Otago, explains.

As people age they can often be affected by 'motivation decline', that is the loss of motivation to learn new things or even engage in everyday activities.  Professor John Reynolds, a neuroscientist from the University of Otago, explains.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.25.354159v1?rss=1 Authors: He, J., Kleyman, M., Chen, J., Alikaya, A., Rothenhoefer, K. M., Ozturk, B. E., Wirthlin, M., Fish, K., Byrne, L. C. T., Pfenning, A. R., Stauffer, W. R. Abstract: The striatum is the neural interface between dopamine reward signals and cortico-basal ganglia circuits responsible for value assignments, decisions, and actions. Medium spiny neurons (MSNs) make up the vast majority of striatal neurons and are traditionally classified as two distinct types: direct- and indirect-pathway MSNs. The direct- and indirect-pathway model has been useful for understanding some aspects of striatal functions, but it accounts for neither the anatomical heterogeneity, nor the functional diversity of the striatum. Here, we use single nucleus RNA-sequencing and Fluorescent In-Situ Hybridization to explore MSN diversity in the Rhesus macaque striatum. We identified MSN subtypes that correspond to the major subdivisions of the striatum. These include dorsal striatum subtypes associated with striosome and matrix compartments, as well as ventral striatum subtypes associated with the shell of the nucleus accumbens. We also describe a cell type that is anatomically restricted to "Neurochemically Unique Domains in the Accumbens and Putamen (NUDAPs)". Together, these results help to advance nonhuman primate studies into the genomics era. The identified cell types provide a comprehensive blueprint for investigating cell type-specific information processing, and the differentially expressed genes lay a foundation for achieving cell type-specific transgenesis in the primate striatum. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.21.348995v1?rss=1 Authors: Liput, D. J., Puhl, H. L., Dong, A., He, K., Li, Y., Lovinger, D. M. Abstract: Several forms of endocannabinoid (eCB) signaling have been described in the dorsal lateral striatum (DLS), however most experimental protocols used to induce plasticity do not recapitulate the firing patterns of striatal-projecting pyramidal neurons in the cortex or firing patterns of striatal medium spiny neurons. Therefore, it is unclear if current models of eCB signaling in the DLS provide a reliable description of mechanisms engaged under physiological conditions. To address this uncertainty, we investigated mechanisms of eCB mobilization following brief synaptic stimulation that mimics in vivo patterns of neural activity in the DLS. To monitor eCB mobilization, the novel genetically encoded fluorescent eCB biosensor, GRABeCB2.0, was expressed in corticostriatal afferents of C57BL6J mice and evoked eCB transients were measured in the DLS using a brain slice photometry technique. We found that brief bouts of synaptic stimulation induce long lasting eCB transients. Inhibition of monoacylglycerol lipase, prolonged the duration of the eCB transient, while inhibition of diacylglycerol lipase inhibited the peak amplitude, suggesting that 2-AG is the predominate eCB generated following brief synaptic stimulation. 2-AG transients were robustly inhibited by AMPA and NMDA receptor antagonists, DNQX and DL-AP5 respectively. Additionally, the 2-AG transient was inhibited by the muscarinic M1 receptor (M1R) antagonist, VU 0255035, and augmented by the M1R positive allosteric modulator, VU 0486846, indicating that acetylcholine (ACh) release is required for efficient 2-AG production. The dopamine D2 receptor (D2R) agonist, quinpirole, inhibited the 2-AG transient. However, in slices from mice lacking D2Rs on cholinergic interneurons (CINs), quinpirole did not inhibit the 2-AG transient, demonstrating that D2Rs on CINs can modulate 2-AG production. The AMPA receptor or NMDA receptor antagonists, DNQX or DL-AP5 respectively, occluded 2-AG augmentation by VU 0486846 suggesting that converging glutamatergic and cholinergic signals are required for efficient 2-AG production following brief synaptic stimulation. Collectively, these data uncover unrecognized mechanisms underlying 2-AG mobilization in the DLS. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.16.299842v1?rss=1 Authors: de Zavalia, N., Schottner, K., Goldsmith, J. A., Solis, P., Ferraro, S., Parent, G., Amir, S. Abstract: The clock gene Bmal1 plays an obligatory role in the generation of circadian rhythms in gene expression, physiology, and behavior in mammals. In mice, perturbations in Bmal1 expression in the brain are associated with loss of circadian rhythmicity and various physiological and behavioral disturbances, including disrupted sleep architecture and deficits in cognitive and affective behaviors. Gene association studies in both humans and animals suggest that Bmal1 may also play a role in the control of appetitive behaviors such as alcohol preference and consumption. Although there is evidence that genes that interact with Bmal1 in the molecular circadian clock, such as Per2 and Clock influence alcohol intake and preference, experimental evidence of a causal role of Bmal1 is lacking. In addition, the specific brain regions where Bmal1 might affect alcohol consumption are not known. We investigated voluntary alcohol consumption in conditional knockout mice that lack BMAL1 protein exclusively in the striatum, which is an important structure in the control of alcohol intake and preference. Particular emphasis was attributed to the investigation of male and female mice because of known sex differences in alcohol intake and preference, and the impact of a sexually dimorphic constitution of circadian clocks on behavior. We found that deletion of BMAL1 from the principal medium spiny neurons (MSNs) of the striatum significantly altered voluntary alcohol intake and preference, without affecting total fluid intake, sucrose preference, body weight, or circadian rhythms in behavior. Strikingly, there were major sex differences in the effect of striatal BMAL1 deletion on alcohol consumption. While striatal BMAL1 deletion augmented alcohol intake and preference in males, the same deletion suppressed intake and preference in females. Interestingly, striatal deletion of PER2, a clock gene that interacts with Bmal1 in the circadian clock, and which has been shown to limit alcohol consumption in mice, mimicked the effect of striatal BMAL1 deletion, albeit only in males. Together, our results reveal that BMAL1 in MSNs of the striatum plays a sexually dimorphic role in the control of alcohol intake in mice, restraining consumption in males, possibly by interacting with PER2, and promoting intake in females, independently of PER2. We therefore hypothesize that a sex-specific mechanism in the function of BMAL1 in MSNs of the striatum regulates differences between male and female mice in the propensity to consume alcohol. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.08.287714v1?rss=1 Authors: Brochard, J., Daunizeau, J. Abstract: Computational investigations of learning and decision making suggest that systematic deviations to adaptive behavior may be the incidental outcome of biological constraints imposed on neural information processing. In particular, recent studies indicate that range adaptation, i.e., the mechanism by which neurons dynamically tune their output firing properties to match the changing statistics of their inputs, may drive plastic changes in the brain's decision system that induce systematic deviations to rationality. Here, we ask whether behaviorally-relevant neural information processing may be distorted by other incidental, hard-wired, biological constraints, in particular: Hebbian plasticity. One of our main contributions is to propose a simple computational method for identifying (and comparing) the neural signature of such biological mechanisms or constraints. Using ANNs (i.e., artificial neural network models) and RSA (i.e., representational similarity analysis), we compare the neural signatures of two types of hard-wired biological mechanisms/constraints: namely, range adaptation and Hebbian plasticity. We apply the approach to two different open fMRI datasets acquired when people make decisions under risk. In both cases, we show that although peoples' apparent indifferent choices are well explained by biologically-constrained ANNs, choice data alone does not discriminate between range adaptation and Hebbian plasticity. However, RSA shows that neural activity patterns in bilateral Striatum and Amygdala are more compatible with Hebbian plasticity. Finally, the strength of evidence for Hebbian plasticity in these structures predicts inter-individual differences in choice inconsistency. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.02.279240v1?rss=1 Authors: Montalban, E., Giralt, A., Taing, L., Nakamura, Y., Martin, C., de Pins, B., Pelosi, A., Goutebroze, L., Castell, L., Wang, W., Daila Neiburga, K., Vestito, L., Nairn, A. C., Valjent, E., Herve, D., Heintz, N., Gambardella Le Novere, N., Greengard, P., Roussarie, J.-P., Girault, J.-A. Abstract: Forebrain dopaminoceptive neurons play a key role in movement, action selection, motivation, and working memory. Their activity is dysregulated in addiction, Parkinson's disease and other conditions. To characterize the diverse dopamine target neuronal populations, we compare translating mRNAs in neurons of dorsal striatum and nucleus accumbens expressing D1 or D2 dopamine receptor and prefrontal cortex expressing D1 receptor. We identify D1/D2 and striatal dorso-ventral differences in the translational and splicing landscapes, which establish the characteristics of dopaminoceptive neurons. Expression differences and network analyses identify novel transcription factors with presumptive roles in these differences. Prostaglandin E2 appears as a candidate upstream regulator in the dorsal striatum, a hypothesis supported by converging functional evidence indicating its role in enhancing D2 dopamine receptor action. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns, and reveals the unforeseen role of prostaglandin E2 in the dorsal striatum. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.31.276253v1?rss=1 Authors: Blackwood, C. A., McCoy, M. T., Ladenheim, B., Cadet, J. L. Abstract: To identify signaling pathways activated by oxycodone self-administration (SA), Sprague-Dawley rats self-administered oxycodone for 20 days using short-access (ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized two hours after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs in the LgA-H rats. GluA3, but not GluA2, expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. Our findings indicate that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation, which promoted increases in striatal gene expression. Our observations offer novel avenues for pharmacological interventions against oxycodone addiction. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.22.262972v1?rss=1 Authors: Kimura, I., Matsumoto, H., Uchida, N., Watabe-Uchida, M. Abstract: Different regions of the striatum regulate different types of behavior. However, how dopamine signals differ across striatal regions and how dopamine regulates different behaviors remain unclear. Here, we compared dopamine axon activity in the ventral, dorsomedial, and dorsolateral striatum, while mice performed in a perceptual and value-based decision task. Surprisingly, dopamine axon activity was similar across all three areas. At a glance, the activity multiplexed different variables such as stimulus-associated values, confidence and reward feedback at different phases of the task. Our modeling demonstrates, however, that these modulations can be inclusively explained by moment-by-moment changes in the expected reward, i.e. the temporal difference error. A major difference between these areas was the overall activity level of reward responses: reward responses in dorsolateral striatum (DLS) were positively shifted, lacking inhibitory responses to negative prediction error. Tenets of habit and skill can be explained by this positively biased dopamine signal in DLS. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.23.216697v1?rss=1 Authors: Piantadosi, S. C., McClain, L. L., Klei, L., Wang, J., Springer, S., Chamberlain, B. L., Lewis, D. A., Devlin, B., Ahmari, S. E. Abstract: Background: Obsessive compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD. However, the transcriptional alterations that could link genetic risk to known structural and functional abnormalities remain mostly unknown. Methods: To assess potential transcriptional changes in the OFC and two striatal regions (caudate nucleus and nucleus accumbens) of OCD subjects relative to unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. Results: In a joint analysis of all three regions, 904 transcripts were differentially expressed between 7 OCD versus 8 unaffected comparison subjects. Region-specific analyses highlight a smaller number of differences, which concentrate in caudate and nucleus accumbens. Pathway analyses of the 904 differentially expressed transcripts showed enrichment for genes involved in synaptic signaling, with these synapse-associated genes displaying lower expression in OCD subjects relative to unaffected comparison subjects. Finally, we estimate that cell type fractions of medium spiny neurons are lower whereas vascular cells and astrocyte fractions are higher in tissue of OCD subjects. Conclusions: Together, these data provide the first unbiased examination of differentially expressed transcripts in both OFC and striatum of OCD subjects. These transcripts encode synaptic proteins more often than expected by chance, and thus implicate the synapse as a vulnerable molecular compartment for OCD. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.19.210690v1?rss=1 Authors: Heltberg, M. L., Awada, H. N., Lucchetti, A., Jensen, M. H., Dreyer, J. K., Rasmussen, R. Abstract: Parkinsons disease (PD) results from a loss of dopaminergic neurons. The age of disease onset, its progression and symptoms vary significantly between patients, pointing to a complex relationship between neuron loss and PD etiology. Yet, our understanding of the clinical variability remains incomplete. Here, we use biophysical modelling to investigate the dopaminergic landscape in the healthy and denervated striatum. Based on currently proposed mechanisms causing PD, we model three distinct denervation patterns, and show notable differences in the dopaminergic network as denervation progresses. We find local and global differences in the activity of two types of striatal neurons as a function of the denervation pattern. Finally, we identify the optimal cellular strategy for maintaining normal dopamine signaling when neurons degenerate within our model. Our results derive a conceptual framework in which the clinical variability of PD is rooted in distinct denervation patterns and forms testable predictions for future PD research. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.17.209601v1?rss=1 Authors: Inokawa, H., Kimura, M., Matsumoto, N., Yamada, H. Abstract: An animal's choice behavior is shaped by the outcome feedback from selected actions in a trial-and-error approach. Tonically active neurons (TANs), presumed cholinergic interneurons in the striatum, are thought to be involved in the learning and performance of reward-directed behaviors, but it remains unclear how TANs are involved in shaping reward-directed choice behaviors based on the outcome feedback. To this end, we recorded activity of TANs from the dorsal striatum of two macaque monkeys (Macaca fuscata; 1 male, 1 female) while they performed a multi-step choice task to obtain multiple rewards. In this task, the monkeys first searched for a rewarding target from among three alternatives in a trial-and-error manner and then earned additional rewards by repeatedly choosing the rewarded target. We found that a considerable proportion of TANs selectively responded to either the reward or the no-reward outcome feedback during the trial-and-error search, but these feedback responses were not observed during repeat trials. Moreover, the feedback responses of TANs were similarly observed in any search trials, without distinctions regarding the predicted probability of rewards and the location of chosen targets. Unambiguously, TANs detected reward and no-reward feedback specifically when the monkeys performed trial-and-error searches, in which the monkeys were learning the value of the targets and adjusting their subsequent choice behavior based on the reward and no-reward feedback. These results suggest that striatal cholinergic interneurons signal outcome feedback specifically during search behavior, in circumstances where the choice outcomes cannot be predicted with certainty by the animals. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.16.207316v1?rss=1 Authors: Moss, M. M., Zatka-Haas, P., Harris, K. D., Carandini, M., Lak, A. Abstract: Midbrain dopamine neurons play key roles in decision-making by regulating reward valuation and actions. These roles are thought to depend on dopamine neurons innervating striatum. In addition to actions and rewards, however, efficient decisions often involve consideration of uncertain sensory signals. The functions of striatal dopamine during sensory decisions remains unknown. We trained mice in a task that probed decisions based on sensory evidence and reward value, and recorded the activity of striatal dopamine axons. Dopamine axons in ventral striatum (VS) responded to bilateral stimuli and trial outcomes, encoding prediction errors that scaled with decision confidence and reward value. By contrast, dopamine axons in dorsal striatum (DS) responded to contralateral stimuli and contralateral actions. Thus, during sensory decisions, striatal dopamine signals are anatomically organized. VS dopamine resembles prediction errors suitable for reward maximization under sensory uncertainty whereas DS dopamine encodes specific combinations of stimuli and actions in a lateralized fashion. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.29.176974v1?rss=1 Authors: Vinner, E., Matzner, A., Belelovsky, K., Bar-Gad, I. Abstract: Motor tics, the hallmark of Tourette syndrome, are modulated by different behavioral and environmental factors. A major modulating factor is the sleep-wake cycle in which tics are attenuated to a large extent during sleep. This study investigates the neural mechanisms underlying tic reduction during sleep in an animal model of chronic tic disorders. We recorded the neuronal activity during spontaneous sleep-wake cycles throughout continuous GABAA antagonist infusion into the striatum. Analysis of video streams and concurrent kinematic assessments indicated tic reduction during sleep in both frequency and intensity. Extracellular recordings in the striatum revealed a dissociation between motor tic expression and their macro-level neural correlates (LFP spikes) during the sleep-wake cycle. LFP spikes persisted during tic-free sleep and did not change their properties despite the reduced behavioral expression. Local, micro-level, activity near the infusion site was phase-locked to the LFP spikes during wakefulness but this locking decreased significantly during sleep. These results suggest that while LFP spikes, which are generated as a result of abnormal and focal disinhibition in the striatum, encode motor tic feasibility, the behavioral expression of tics requires local striatal neural activity entrained to the LFP spikes, leading to the propagation of the activity to downstream targets and consequently their motor expression. These findings point to a possible mechanism for the modulation of tic expression in TS patients during sleep and potentially during other behavioral states. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.21.163618v1?rss=1 Authors: Huntington, T. E., Srinivasan, R. Abstract: Astrocytes govern critical aspects of brain function via Ca2+ signals, the majority of which associate with mitochondria. However, little is known with regard to in situ sources, kinetics or mechanisms of Ca2+ influx in astrocytic mitochondria. To address this knowledge gap, we expressed the genetically encoded calcium indicator, GCaMP6f within the mitochondrial matrix of adult mouse astrocytes in the dorsolateral striatum (DLS) and hippocampus (HPC). We found spontaneous Ca2+ events in astrocytic mitochondria with subcellular differences between somatic, branch, and branchlet mitochondria, as well as inter-regional differences between astrocytes in the DLS and HPC. We also found a strong dependency of spontaneous mitochondrial Ca2+ fluxes on endoplasmic reticulum stores, the surprising lack of a major role for the mitochondrial calcium uniporter, MCU, and dual mitochondrial Ca2+ responses with multiple neurotransmitter agonists. Together, our findings provide a foundational understanding of mechanisms for Ca2+ influx in astrocytic mitochondria within disease-relevant brain regions. Copy rights belong to original authors. Visit the link for more info

In towards motivation the dopamine system is primarily active. Dopamine determines how the brain processes reward and hence what is motivating to pursue. ... There is a system of brain regions that are important: one is the nucleus accumbens, another is the Striatum and the third is the ventral medial prefrontal cortex. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.12.090175v1?rss=1 Authors: Colizoli, O., de Gee, J. W., van der Zwaag, W., Donner, T. H. Abstract: Significant progress has been made in ultra-high field functional magnetic resonance imaging (fMRI) at 7 Tesla (T). While fMRI at 7 T promises a general increase in sensitivity compared to lower field strengths, the benefits may be most pronounced for specific applications. The current study aimed to evaluate the relative benefit of 7 T over 3 T fMRI for the assessment of task-evoked fMRI responses in different brain regions. We compared the amplitude of task-evoked responses between 3 T and 7 T measured from the same human participants. Participants performed a challenging random dot motion discrimination task with delayed monetary feedback, which animal physiology has linked to several cortical and subcortical structures including extrastriate (dorsal) visual cortical areas, the striatum, and the brainstem including dopaminergic midbrain nuclei. We quantified the evoked fMRI responses in each of these brain regions during the decision interval and the post-feedback interval of the task, and compared them between brain regions and field strengths. The dependence of response amplitudes on field strength during the decision interval differed between cortical, striatal, and brainstem regions, with a generally bigger 7 T vs. 3 T benefit in subcortical (in particular brainstem) structures. We also found stronger differential responses during easy than hard decisions at 7 T for the dopaminergic nuclei, possibly reflecting reward expectation. Our results demonstrate the potential of 7 T fMRI for illuminating the contribution of small brainstem nuclei to the orchestration of cognitive computations in the human brain. Copy rights belong to original authors. Visit the link for more info

Restricted interests and repetitive behaviors are hallmarks of autism. They can take many forms: Some autistic people flap their arms or rock back and forth; others ritualistically line up objects or insist on a rigid daily schedule.

Associated primarily with its role in movement, the striatum may also influence the social difficulties of autistic people.

Nathan talks about his experience at the Odyssey of the Mind World Finals last week! Odyssey is a critical thinking program where kids of all ages from all around the world gather to compete in a test of wits and you guessed it. Problem Solving! Also, learn about the parts of the brain that facilitate problem-solving. You don't wanna miss out on this one!Scrubcaps Every Monday!--> Visit https://www.brainontheloose.com for more awesome stuff!--> Follow me on Instagram! @scrubcaps_brainonthelooseSupport the show (http://patreon.com/ Nathanhidajatscrubcaps)

Learn about why your brain treats hunger for knowledge like hunger for food; why the unexplored blue holes of Andros in the Bahamas is home to one of the most unique ecosystems on Earth; and folie à deux, a type of mental illness that can be shared and spread between people. In this podcast, Cody Gough and Ashley Hamer discuss the following stories from Curiosity.com to help you get smarter and learn something new in just a few minutes: Your Brain Treats Hunger for Knowledge Like Hunger for Food — https://curiosity.im/2rMu072 Andros, Bahamas Has More Than 200 "Blue Holes" — And They're Mostly Unexplored — https://curiosity.im/2rMW0r2 Folie à Deux Is the Psychosis You Share With the One You Love — https://curiosity.im/2rMtXrS If you love our show and you're interested in hearing full-length interviews, then please consider supporting us on Patreon. You'll get exclusive episodes and access to our archives as soon as you become a Patron! https://www.patreon.com/curiositydotcom Download the FREE 5-star Curiosity app for Android and iOS at https://curiosity.im/podcast-app. And Amazon smart speaker users: you can listen to our podcast as part of your Amazon Alexa Flash Briefing — just click “enable” here: https://curiosity.im/podcast-flash-briefing.

V dnešnom podcaste si povieme o tom, prečo vlastne nestrieľame nukleárny odpad do Slnka a o tom, či robí láska ľudí hlúpejšími. TémyZdroje Intro  Prečo nestrieľame nukleárny odpad do Slnka?  Robí láska ľudí hlúpejšími?  Fakt a fikcia Outro CAN WE LAUNCH NUCLEAR WASTE INTO THE SUN? Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density in Striatum and Increased Subjective Happiness Is a Drunk Witness a Bad Witness? The Hard Truth about the Rhino Horn “Aphrodisiac” Market Shoulder pad foam layer plays role in fewer concussions, researchers find

This lecture is the second of two on the corpus striatum, including discussion of the anatomy, connections and associated diseases.

This lecture is the first of two on the corpus striatum that includes a summary of the limbic system and introduces the corpus striatum.

Interview with Deepak K. Sarpal, MD, author of Antipsychotic Treatment and Functional Connectivity of the Striatum in First-Episode Schizophrenia

William Pryor and Srinivasa Subramaniam report that a mutant form of huntingtin that is associated with early-onset Huntington's disease promotes anabolic signaling that contributes to disease symptoms in mice.

What's the role of the striatum, in changes in cognition and behaviour in neurodegeneration? Michael Hornberger, University of Cambridge, explains why it may be more pivotal than we currently think.And how best to support patients just diagnosed with multiple sclerosis, who are facing difficult decisions around their treatment? Sascha Köpke, University of Lübeck, discusses the results of his trial comparing two programmes.Read the papers, for free:Beyond and below the cortex: the contribution of striatal dysfunction to cognition and behaviour in neurodegeneration http://goo.gl/IZJi2oEvidence-based patient information programme in early multiple sclerosis: a randomised controlled trial http://goo.gl/nQdJ15

Dave and Tamler begin with a brief, heartfelt discussion about the Boston Bombings.  Tamler talks about why Patriots' Day and the Boston Marathon mean so much to a kid growing up in Boston.  They speculate a bit about the motive behind the attack and ask why the perpetrators didn't come out and claim responsibility.  In the second and third segments, Molly Crockett joins us to challenge Fiery Cushman for the prize of classiest episode ever.  She tells us about her research on the effects of serotonin depletion on retributive behavior, and how it was reported as "Chocolate and Cheese help you make better decisions" in the popular media.  We talk about the responsibility that scientists have to make sure that their studies are reported properly, and how brain research can (despite David's previous claims) help shed light on human nature and behavior.  Also: Tamler mangles the pronunciation of roughly 14 brain regions, Dave yearns for the days when restrictions of human experimentation were non-existent, and both Dave and Tamler subtly and then not so subtly try to get Molly to hook them up with...molly.  Enjoy!LinksDirty Water by the Standells [youtube.com]Patriots' Day [wikipedia.org]Molly Crockett  [mollycrockett.com]Crockett, M. J., Clark, L., Tabibnia, G., Lieberman, M. D., & Robbins, T. W. (2008). Serotonin modulates behavioral reactions to unfairness. Science, 320, 1739.Serotonin [wikipedia.org]Striatum [wikipedia.org]DMT [wikipedia.org]   Special Guests: Fiery Cushman and Molly Crockett.

MDS presents the latest research and findings from the field of Movement Disorders. Abstracts of articles from the Society Journal, Movement Disorders, are taken from the February 2013 (Vol. 28, Issue 2) issue.

How does nicotine open a gateway to cocaine addiction? A new study indicates that nicotine primes the brain for cocaine - by altering the structure of a gene linked to learning, memory and addiction. Like this podcast? Please help us by supporting the Naked Scientists

How does nicotine open a gateway to cocaine addiction? A new study indicates that nicotine primes the brain for cocaine - by altering the structure of a gene linked to learning, memory and addiction. Like this podcast? Please help us by supporting the Naked Scientists

Solche Meldungen lesen wir öfter: der Optimismus liegt zwischen ACC und Amygdala, die Gerechtigkeit in PFC und Striatum. Hier feiern wir einige dieser Spezialisten und beschreiben und hinterfragen den Weg ihrer Entdeckung. Dazu: soziales Mimikry!

„Investigation of neurologic outcome and cerebral inflammation after deep hypothermic circulatory arrest in the rat: The impact of the rewarming rate” Despite considerable progress in medicine, and the adapt use of CPB with DHCA, congenital heart defects are still considered a challenge for surgery. Today`s scientific research focuses on CPB with DHCA and the possible cerebral inflammatory reaction, contributing to the often adverse neurologic and neurocognitive outcome following CPB with DHCA. Aim o f this study is to investigate the impact of the rate and duration of rewarming have on postoperative neurologic function, histologic outcome and cerebral inflammatory reaction in a clinically relevant animal model of CPB with 45 min of DHCA in the rat. 20 male Sprague Dawley rats (330 – 390 g) were anaesthetized, endotracheally intubated and ventilated with 2 to 2.5 Vol % Isoflurane in 40 Vol % O2. For pain management all animals received repititive 5µg boli of Fentanyl. Animals were surgically cannulated as follows: the A. sacralis mediana for arterial inflow during CPB, the taking of blood samples and drug administration. The A. epigastrica superficialis for blood pressure monitoring and the V. jugularis externa and V. cava cranialis for venous drainage during CPB. During the cooling phase anaesthesia was maintained with 0.8 to 1Vol % Isoflurane and Cisartracurium was given additionally for muscle relaxation (1,6mg/h). To cool rats down to a rectal temperature of 15 – 18 °C within 30 min, cooling blankets, ice bags and a heat exchanger in the oxygenator were used. At 15 – 18 °C, CPB and anaesthesia were terminated for 45 minutes and the venous drainage was opened every ten minutes to allow the animals to exsanguinate to prevent a right heart dilatation. Rats were then randomly assigned to one of two rewarming groups (n = 10): with reinstitution of CPB and anaesthesia, one group was rewarmed slowly over 40 minutes and a second group fast over 20 minutes back to a rectal temperature of 35.5 °C. When reaching 35.5 °C, animals were weaned from CPB, and anaesthesia was maintained for one hour folllowing CPB. During that time the blood left in the circuit was collected, centrifuged, adjusted with HES and calcium to a hematocrit below 50% and returned to raise the animal`s hematocrit above 30%. Anaesthesia was terminated one hor following CPB. Animals were extubated when showing sufficient spontaneous breathing and allowed to recover under observation in an oxygen enriched environment. Rats were neurologically tested one day prior to CPB with DHCA as well as on the postoperative day. 24 hours following the end of CPB, animals were sacrificed, their brains removed and deep frozen (-70 °C) for further analysis. H&E staining was performed using slices taken at bregma –0.3 and –3.3 to investigate the histological damage in the Gyrus cinguli, Striatum, motor cortex, Hippocampus and Vermis. NF-kB- positive neurons were labelled with an immunhistochemical double staining and counted using light microscopy. Inflammatory parameters TNF-α, COX-2 and I-kB were evalueted using Wetsern Blotting. For the first time this study compares the neurologic outcome following two different rewarming protocols after DHCa in a clinically relevant animal model of CPB with DHCA. Unexpectedly, a better neurologic outcome is seen after fast rewarming. Although results for histology and immunehistochemistry show higher amounts of eosinohilic and NF-kB- positive neurons in this group. Western Blot also shows increased levels of inflammatory parameters COX-2 and I-kB in the fast rewarming group. These findings suggest that the rewarming rate alone is not the chief cause for an adverse neurological out-come after CPB with DHCA. Further studies concerning the mechanisms leading to adverse neurologic outcome and cerebral inflammatory reaction following CPB with DHCA are required.

In dieser Arbeit wurde gezeigt, dass die Zellen des Glomus caroticum der Ratte alle notwendigen Komponenten zur Biosynthese, Speicherung und Freisetzung von Dopamin und Histamin besitzen und diese Transmitter bei Hypoxie freisetzen können. Erstmals wurde hier Histamin als Transmitter im Glomus caroticum nachgewiesen: es wurde gezeigt, dass die Sensorzellen des Glomus caroticum das Histamin synthetisierende Enzym exprimieren. Die Speicherung von Histamin in Vesikeln erfolgt mit Hilfe eines vesikulären Monoamintransporters (VMAT2). Bisher bekannte immunhistochemische Ergebnisse über die Expression dieses Transportproteins in den Sensorzellen konnten bestätigt und mittels RT-PCR-Untersuchungen belegt werden. Ferner wurde nachgewiesen, dass die Sensorzellen auch über wichtige Komponenten des Exozytoseapparates verfügen. Darüber hinaus zeigten RT-PCR- Untersuchungen, dass im Glomus caroticum die mRNA der Histaminrezeptoren H1, H2 und H3 exprimiert wird. Die Menge an Histamin im Glomus caroticum wurde mittels Radioimmunoassay bestimmt. Im Glomus caroticum ist mehr Histamin enthalten als in anderen Geweben der Ratte, und die Menge an Histamin ist um ein Vielfaches größer als die Menge des im Glomus caroticum enthaltenen Dopamins. In vitro Experimente zeigten, dass die Freisetzung von Histamin aus dem Glomus caroticum durch Hypoxie verstärkt wird. Eine vermehrte Freisetzung bei Hypoxie konnte amperometrisch auch für Dopamin bestätigt werden. Es wurde hier zum ersten Mal beschrieben, dass ein Zelltyp zwei verschiedene Amine als Transmitter nutzt. Damit spielt sowohl Dopamin als auch Histamin eine wesentliche Rolle bei der Kontrolle der Sauerstoffversorgung des Organismus und, aufgrund der Lage des Glomus caroticum, besonders des Gehirns. Mit dem Nachweis von Expression und Aktivität des limitierenden Enzyms für die Tetrahydrobiopterin-Synthese wurde gezeigt, dass das Glomus caroticum sämtliche für die Dopaminsynthese notwendigen Schritte selbst durchführen kann. Damit erfüllt das Glomus caroticum die notwendigen Eigenschaften für eine erfolgreiche Autotransplantation in das Striatum bei Morbus Parkinson.

Die vorliegende Arbeit hat die Bedeutung von Leukozyten-Endothelinteraktionen bei der globalen zerebralen Ischämie zum Thema. Weiße Blutkörperchen besitzen ein enormes pathophysiologisches Potenzial, das bei Überaktivierung oder Fehlregulation für viele Symptome von Patienten mit entzündlichen Erkrankungen und für den Untergang von Gewebe verantwortlich ist. Leukozyten sind Mediatorzellen des sekundären Gewebeschadens bei der Ischämie und nachfolgenden Reperfusion, wie für viele Organe gezeigt wurde. Auch bei der globalen zerebralen Ischämie wird eine pathogenetische Rolle von Leukozyten – bislang kontrovers – diskutiert. Zahlreiche Befunde sind aus klinischen und experimentellen Studien hervorgegangen, die sowohl für als auch gegen eine Beteiligung von aktivierten Leukozyten am ischämischen Hirnschaden sprechen. Die Bedeutung von Leukozyten-Endothelinteraktionen und von Veränderungen der zerebralen Mikrozirkulation sind in diesem Zusammenhang nach wie vor nicht geklärt. Das Ziel der vorliegenden Arbeit war daher, das Verhalten von Leukozyten und die zerebrale Mikrozirkulation bei der globalen zerebralen Ischämie zu untersuchen, einschließlich der morphologischen und funktionellen Auswirkungen von pathologischen Veränderungen. Für diese Untersuchungen wurde erstmals ein chronisches Modell der globalen zerebralen Ischämie mit Mongolischen Wüstenrennmäusen etabliert, das die Quantifizierung von Parametern der Mikrozirkulation, insbesondere von Leukozyten-Endothelinteraktionen, ermöglichte, sowie von funktionellen Defiziten und von Nervenzelluntergängen. Die Präparation eines geschlossenen Schädelfensters mit Erhalt einer intakten Dura mater und die einfache, wenig traumatische, extrakranielle, reversible Unterbindung beider Halsschlagadern zur Induktion der Ischämie erlaubte das Überleben der Versuchstiere. Somit konnte die intravitale Fluoreszenzmikroskopie zur Analyse der zerebralen Mikrozirkulation mit der Erhebung morphologischer Parameter anhand histologischer Untersuchungen und von funktionellen Defiziten bei denselben Versuchstieren unter chronischen Bedingungen kombiniert werden. Die beidseitige, 15-minütige Karotisokklusion führte zur ausgeprägten Ischämie des Großhirns gefolgt von einer, auch in anderen Untersuchungen beschriebenen, typischen postischämischen Hyper- und verzögerten Hypoperfusion des Gehirns. Diese Änderungen der Hirndurchblutung konnten in enger Korrelation mit Laser-Doppler Fluxmetrie und Bestimmung der arteriovenösen Transitzeit bestätigt werden. Die einfache Berechnung der arteriovenösen Transitzeit wurde als Verfahren validiert die regionale Durchblutung wiederholt und ohne Traumatisierung durch Intravitalmikroskopie zu bestimmen. Die globale zerebrale Ischämie führt zu einer eher kurzen Aktivierung von Leukozyten-Endothelinteraktionen mit stetem Anstieg der Zahl rollender und adhärenter Leukozyten in postkapillären Venolen in der frühen Reperfusionsphase bis 3 Stunden nach dem Insult. Sechs Stunden nach Reperfusionsbeginn nahm die Leukozytenaktivierung wieder ab, nach 7 Stunden war sie auf das Niveau von Kontrolltieren abgefallen. Die Aktivierung war unabhängig vom Status der mikrovaskulären Perfusion; sie konnte in den histologischen Schnitten mit Leukozyten-spezifischer Färbung auch in den tiefen, parenchymatösen Strukturen nachgewiesen werden. Unter Kontrollbedingungen fanden in den Hirngefäßen keine Interaktionen von Leukozyten mit dem Endothel statt, eine weitere Beobachtung, die wie der Erhalt der Blut-Hirnschrankenintegrität für die Qualität des Modells spricht. Ein andauernder Verschluss von Kapillaren durch Leukozyten – Plugging – konnte nicht beobachtet werden. Ebenso wenig wurde eine Veränderung der Zahl perfundierter Kapillaren in der postischämischen Phase gefunden, die Kapillardichte blieb nach dem ischämischen Insult unverändert. Eine globale Ischämie des Gehirns führt zu neurologischen Defiziten, Änderungen des Verhaltens und zu einer Abnahme des Körpergewichts. Vier Tage nach Insult wurde ein erheblicher Untergang von selektiv vulnerablen Nervenzellen im Kortex, Hippocampus und Striatum festgestellt, wobei das Ausmaß des Zellverlusts im Kortex mit dem Auftreten der funktionellen Ausfälle korreliert war. Ein statistischer Zusammenhang zwischen dem Ausmaß der Leukozytenaktivierung und des neurologischen Defizits oder dem Verlust an Körpergewicht konnte nicht festgestellt werden. Ebensowenig konnte bestätigt werden, dass vermehrtes Vorkommen von Rollern und Stickern den ischämischen Gewebeschaden vergrößert. Im Gegenteil – wider alle Erwartungen – war das Ausmaß der Leukozytenaktivierung direkt proportional zur Anzahl überlebender Neurone in vulnerablen Hirnarealen. Dieser Zusammenhang war als Trend in fast allen Hirnarealen erkennbar und erreichte in einigen sogar signifikantes Niveau. Die Ergebnisse der vorliegenden Arbeit zeigen, dass die globale zerebrale Ischämie Leukozyten-Endothelinteraktionen aktiviert – allerdings nur vorrübergehend. Eine Beteiligung der Leukozytenaktivierung an der postischämischen Minderperfusion des Gehirns war nicht nachweisbar. Die Ausgangshypothese, dass aktivierte Leukozyten den ischämischen Hirnschaden verstärken, konnte nicht bestätigt werden. Das Vorliegen eines statistischen Zusammenhangs zwischen dem Ausmaß der Leukozytenaktivierung und der Zahl von überlebenden Nervenzellen könnte neue Hypothesen generieren; z. B. könnten aktivierte Leukozyten neuroprotektive Eigenschaften haben und/oder regenerative Prozesse im postischämischen Gehirn unterstützen. Zusammengefasst kommt es in diesem experimentellen Modell einer globalen zerebralen Ischämie beim Gerbil zu einer transitorischen Aktivierung von Leukozyten-Endothelinteraktionen, jedoch ohne dass dadurch der sekundäre Hirnschaden verstärkt würde. Diese Beobachtung ist neu – sie kann hierzu vorliegende widersprüchliche Befunde über die Bedeutung von Leukozyten-Endothelinteraktionen bei der globalen Ischämie besser verständlich machen.

Diese Arbeit befasst sich mit der Embryonalentwicklung des Vorderhirns bei der Maus. Es werden die zellulären und molekularen Mechanismen untersucht, die eine distinkte Entwicklung von zwei benachbarten Regionen im Telencephalon, dem zerebralen Cortex und dem Striatum, ermöglichen. Es wird gezeigt, dass Zellen, die im Cortex entstehen, innerhalb des Cortex wandern, aber nicht über die Grenze in den Striatum hinein wandern können. Auf der anderen Seite können Zellen aus dem Striatum in den Cortex hinein wandern. Die Untersuchung dieser Zellwanderung in Mausmutanten zeigt, dass die Transkriptionsfaktoren Ngn2 und Pax6, die nur von den corticalen und Grenz-Zellen exprimiert werden, notwendig sind für die Restriktion der Zellen innerhalb des Cortex. Pax6 muss auch anwesend sein, um auch die Wanderung der striatalen Zellen gering zu halten. Weiterhin wird gezeigt, dass die interzelluläre Kommunikation via Gap-Junctions an der Grenzregion zwischen Cortex und Striatum unterbrochen wird. Somit weist die cortico-striatale Grenze die gleichen Merkmale wie andere Grenzen in der Embryonalentwicklung von Vertebraten oder auch von Insekten: Eine distinkte Genexpression, die Restriktion der Zellwanderung, und die Unterbrechung der interzellulären Kommunikation.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.20.051284v1?rss=1 Authors: Scavuzzo, C. J., Newman, L. A., Gold, P. E., Korol, D. L. Abstract: Peripheral and central administration of glucose potently enhance cognitive functions. The present experiments examined changes in brain extracellular glucose levels while rats were trained to solve hippocampus-sensitive place or striatum-sensitive response learning tasks for food or water reward. During the first minutes of either place or response training, extracellular glucose levels declined in both the hippocampus and striatum, an effect not seen in untrained, rewarded rats. Subsequently, glucose increased in both brain areas under all training conditions, approaching asymptotic levels ~15-25 min into training. Compared to untrained-food controls, training with food reward resulted in significant increases in the hippocampus but not striatum; striatal levels exhibited large increases to food intake in both trained and untrained groups. In the rats trained to find water, glucose levels increased significantly above the values seen in untrained rats in both hippocampus and striatum. The present findings suggest that decreases in glucose early in training might reflect an increase in brain glucose consumption, perhaps triggering increased brain uptake of glucose from blood, as evident in the increases in glucose late in training. Together with past findings measuring lactate levels under the same conditions, the initial decreases in glucose may also stimulate increased production of lactate from astrocytes to support neural metabolism directly and/or to act as a signal to increase blood flow and glucose uptake into the brain. Copy rights belong to original authors. Visit the link for more info