841 research outputs found

    Screening of squirrel monkeys /Saimiri sciureus/ for vestibular function studies

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    Pathological changes and morphology of squirrel monkeys determined in screening for vestibular function studie

    Pausing to Regroup: Thalamic Gating of Cortico-Basal Ganglia Networks

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    How the cholinergic and dopaminergic systems of the striatum interact and how these interface with the massive neocortical input to the striatum are classic questions of cardinal interest to neurology and psychiatry. In this issue of Neuron, Ding and colleagues show that a key to these puzzles lies in the thalamic inputs to the striatum targeting its cholinergic interneurons

    Differential Dynamics of Activity Changes in Dorsolateral and Dorsomedial Striatal Loops during Learning

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    The basal ganglia are implicated in a remarkable range of functions influencing emotion and cognition as well as motor behavior. Current models of basal ganglia function hypothesize that parallel limbic, associative, and motor cortico-basal ganglia loops contribute to this diverse set of functions, but little is yet known about how these loops operate and how their activities evolve during learning. To address these issues, we recorded simultaneously in sensorimotor and associative regions of the striatum as rats learned different versions of a conditional T-maze task. We found highly contrasting patterns of activity in these regions during task performance and found that these different patterns of structured activity developed concurrently, but with sharply different dynamics. Based on the region-specific dynamics of these patterns across learning, we suggest a working model whereby dorsomedial associative loops can modulate the access of dorsolateral sensorimotor loops to the control of action.National Institutes of Health (U.S.) (MH60379)United States. Office of Naval Research (N000140410208)Stanley H. and Sheila G. Sydney FundEuropean Union (Grant 201716)McGovern Institute for Brain Research at MIT (Fellowship

    The effect of changing the resultant linear acceleration relative to the subject on nystagmus generated by angular acceleration

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    Effect of changing resultant linear acceleration relative to human subject on nystagmus generated by angular acceleratio

    Striatal Volume Predicts Level of Video Game Skill Acquisition

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    Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.United States. Office of Naval Research (grant number N00014-07-1-0903

    Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance

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    The acquisition of language and speech is uniquely human, but how genetic changes might have adapted the nervous system to this capacity is not well understood. Two human-specific amino acid substitutions in the transcription factor forkhead box P2 (FOXP2) are outstanding mechanistic candidates, as they could have been positively selected during human evolution and as FOXP2 is the sole gene to date firmly linked to speech and language development. When these two substitutions are introduced into the endogenous Foxp2 gene of mice (Foxp2[superscript hum]), cortico-basal ganglia circuits are specifically affected. Here we demonstrate marked effects of this humanization of Foxp2 on learning and striatal neuroplasticity. Foxp2[superscript hum/hum] mice learn stimulus–response associations faster than their WT littermates in situations in which declarative (i.e., place-based) and procedural (i.e., response-based) forms of learning could compete during transitions toward proceduralization of action sequences. Striatal districts known to be differently related to these two modes of learning are affected differently in the Foxp2[superscript hum/hum] mice, as judged by measures of dopamine levels, gene expression patterns, and synaptic plasticity, including an NMDA receptor-dependent form of long-term depression. These findings raise the possibility that the humanized Foxp2 phenotype reflects a different tuning of corticostriatal systems involved in declarative and procedural learning, a capacity potentially contributing to adapting the human brain for speech and language acquisition.Nancy Lurie Marks Family FoundationSimons Foundation (Autism Research Initiative Grant 137593)National Institutes of Health (U.S.) (Grant R01 MH060379)Wellcome Trust (London, England) (Grant 075491/Z/04)Wellcome Trust (London, England) (Grant 080971)Fondation pour la recherche medicaleMax Planck Society for the Advancement of Scienc

    Human Substantia Nigra Neurons Encode Unexpected Financial Rewards

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    The brain's sensitivity to unexpected outcomes plays a fundamental role in an organism's ability to adapt and learn new behaviors. Emerging research suggests that midbrain dopaminergic neurons encode these unexpected outcomes. We used microelectrode recordings during deep brain stimulation surgery to study neuronal activity in the human substantia nigra (SN) while patients with Parkinson's disease engaged in a probabilistic learning task motivated by virtual financial rewards. Based on a model of the participants' expected reward, we divided trial outcomes into expected and unexpected gains and losses. SN neurons exhibited significantly higher firing rates after unexpected gains than unexpected losses. No such differences were observed after expected gains and losses. This result provides critical support for the hypothesized role of the SN in human reinforcement learning

    Sonic Hedgehog Is a Chemoattractant for Midbrain Dopaminergic Axons

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    Midbrain dopaminergic axons project from the substantia nigra (SN) and the ventral tegmental area (VTA) to rostral target tissues, including the striatum, pallidum, and hypothalamus. The axons from the medially located VTA project primarily to more medial target tissues in the forebrain, whereas the more lateral SN axons project to lateral targets including the dorsolateral striatum. This structural diversity underlies the distinct functions of these pathways. Although a number of guidance cues have been implicated in the formation of the distinct axonal projections of the SN and VTA, the molecular basis of their diversity remains unclear. Here we investigate the molecular basis of structural diversity in mDN axonal projections. We find that Sonic Hedgehog (Shh) is expressed at a choice point in the course of the rostral dopaminergic projections. Furthermore, in midbrain explants, dopaminergic projections are attracted to a Shh source. Finally, in mice in which Shh signaling is inactivated during late neuronal development, the most medial dopaminergic projections are deficient

    Repeated Methamphetamine Administration Differentially Alters Fos Expression in Caudate-Putamen Patch and Matrix Compartments and Nucleus Accumbens

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    Background: The repeated administration of psychostimulant drugs produces a persistent and long-lasting increase (β€˜β€˜sensitization’’) in their psychomotor effects, which is thought to be due to changes in the neural circuitry that mediate these behaviors. One index of neuronal activation used to identify brain regions altered by repeated exposure to drugs involves their ability to induce immediate early genes, such as c-fos. Numerous reports have demonstrated that past drug experience alters the ability of drugs to induce c-fos in the striatum, but very few have examined Fos protein expression in the two major compartments in the striatumβ€”the so-called patch/striosome and matrix. Methodology/Principal Findings: In the present study, we used immunohistochemistry to investigate the effects of pretreatment with methamphetamine on the ability of a subsequent methamphetamine challenge to induce Fos protein expression in the patch and matrix compartments of the dorsolateral and dorsomedial caudate-putamen and in the ventral striatum (nucleus accumbens). Animals pretreated with methamphetamine developed robust psychomotor sensitization. A methamphetamine challenge increased the number of Fos-positive cells in all areas of the dorsal and ventral striatum. However, methamphetamine challenge induced Fos expression in more cells in the patch than in the matrix compartment in the dorsolateral and dorsomedial caudate-putamen. Furthermore, past experience with methamphetamine increased the number of methamphetamine-induced Fos positive cells in the patch compartment of the dorsal caudate putamen, but no
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