シンポジウム（Symposium）

Symposium Linking Neural Circuits and Function to Behaviour シンポジウム Linking Neural Circuits and Function to Behaviour

7月27日（土）8:50～9:15　第3会場（朱鷺メッセ　2F　メインホールB） 3S03m-1 VCAM1 Label a Subpopulation of Neural Stem Cells in Adult Hippocampus and Functional Link to Spatial Memory Xiao-Ling Hu（Hu Xiao-Ling）^1,2，Dan-Ying Wang（Wang Dan-Ying）^1,2，An-Feng Luo（Luo An-Feng）^1,2，Qing-Ran Bai（Bai Qing-Ran）⁴，Qin Shen（Shen Qin）⁴，Xiao-Min Wang（Wang Xiao-Min）^1,2,3 ¹School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; ²Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing 100069, China; ³Beijing Institute for Brain Disorders, Beijing 100069, China; ⁴Brain and Spinal Cord Innovative Research Center of Tongji Hospital, School of Life Sciences and Technology Tongji University, Shanghai 200065, China Adult hippocampal dentate gyrus (DG) accommodates adult neural stem cells (NSCs) which capable of generating new-born neuron throughout adulthood. The adult NSCs are not homogeneous population, but cells with variety of subpopulation marked by GFAP, Nestin or Sox2. However, currently, few of adult hippocampal NSCs could be identified by specific cell-surface marker. Here, we report a novel NSCs cell surface-expressing marker VCAM1, which co-labeling with GFAP, Nestin and Sox2, representing a small subpopulation of NSCs in adult hippocampus. Interestingly, most of VCAM1 cells were largely quiescent instead of active proliferating. By lineage tracing of VCAM1 cells in adult DG with virus injection in Ai14 reporter mice, we confirmed that VCAM1 cells in SGZ were capable of generating neuron, astrocytes, and oligodentrocytes, indicating a characteristic of multipotency. Depletion of VCAM1 cells from embryonic stage or adult stage led to impaired spatial learning and memory, simultaneously with decreased proliferation of SGZ cells and loss of DG neurons. Our results reveal that VCAM1 labels a small subpopulation of adult NSCs and served as quiescent retaining cells marker in adult hippocampus. The multipotent capacity of generating three types of neural cells might link its function to spatial memory.		7月27日（土）9:15～9:45　第3会場（朱鷺メッセ　2F　メインホールB） 3S03m-2 Linking emotion to motion: an open cortico-basal ganglia loop allows limbic control over motor output Sho Aoki（Aoki Sho）^1,2,3,4，Jared B Smith（Smith Jared B）¹，Hao Li（Li Hao）¹，Xunyi Yan（Yan Xunyi）¹，Masakazu Igarashi（Igarashi Masakazu）^2,4，Patrice Coulon（Coulon Patrice）⁵，Jeffery R Wickens（Wickens Jeffery R）²，Tom JH Ruigrok（Ruigrok Tom JH）³，Xin Jin（Jin Xin）¹ ¹Salk Institute for Biological Studies ²Okinawa Inst. of Science and Technology ³Erasmus Medical Center Rotterdam ⁴Japan Society for the Promotion of Science ⁵Institut des Neurosciences de la Timone Cortico-basal ganglia-thalamocortical loops are conceived as parallel circuits that process limbic, associative, and sensorimotor information. Whether and how these functionally distinct loops interact remains unknown. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops. Indeed, these loops were largely closed within each functional domain. Unexpectedly, we discovered a novel unidirectional influence of the limbic loop onto the motor loop via ventral striatum-substantia nigra pars reticulata (SNr)-motor thalamus circuitry. The anatomical projection from ventral striatum functionally inhibits nigro-motor thalamic neurons in the SNr in slice electrophysiology. In vivo optogenetic stimulation of ventral or dorsolateral striatum-SNr pathway modulates the activity of the medial prefrontal cortex and motor cortex, respectively. However, whereas the optogenetic activation of the dorsolateral striatum-SNr pathway exerts little impact on the medial prefrontal cortex, the activation of the ventral striatum-SNr pathway effectively alters the activity of the motor cortex. We here unveil an open cortico-basal ganglia loop by which limbic information could modulate motor output through ventral striatum control of the motor cortex. These results also have important implications in a wide range of neurological and psychiatric diseases from obsessive-compulsive disorder to anxiety and depression where the limbic control of action is compromised.

7月27日（土）9:45～10:10　第3会場（朱鷺メッセ　2F　メインホールB） 3S03m-3 Neural circuit that drives fear and its extinction Roger Marek（Marek Roger） The University of Queensland Fear conditioning is an established Pavlovian learning paradigm. The amygdala, medial prefrontal cortex (mPFC) and hippocampus, three structures with extensive inter-connectivity, are key elements of the circuits that mediate emotional learning. While both fear learning and extinction are initiated in the amygdala, expression of fear and its extinction also engage the hippocampus, and mPFC. In rodents, the prelimbic (PL) and infralimbic (IL) sub-regions of the mPFC have been implicated in regulating different stages of fear learning, with the PL implicated in fear expression and the IL in fear extinction. Recent findings have started to question the distinct role of these prefrontal sub-regions in selectively modulating fear learning and extinction. This is firstly apparent by the identification of a deep-layer specific intra-PFC connection from the PL to the IL to enhance extinction. Moreover, we have recently identified the precise neural circuits in the mPFC that mediate contextual information from the hippocampus to the PFC. The findings revealed that the hippocampus sends a dominant projection to parvalbumin-positive interneurons in the IL that shunts IL activity to allow the relapse of fear. I will summarize our recent findings and discuss the role of the PFC and hippocampus for the expression of fear-related behaviours, and will allude to future studies that are necessary in order to comprehend prefrontal function in fear and extinction.		7月27日（土）10:10～10:35　第3会場（朱鷺メッセ　2F　メインホールB） 3S03m-4 Ketamine, burst, glia and depression Yan Yang（Yang Yan），Hui Yi Cui（Cui Hui Yi），Ning Kang Sang（Sang Ning Kang），Yan Yi Dong（Dong Yan Yi） Zhejiang University The discovery of the rapid antidepressant effects of the N–methyl–D–asparate(NMDA) receptor antagonist ketamine is arguably elevates mood so quickly has remained elusive. A single administration of ketamine elicits fast and sustained antidepressant effects both in human clinical trails and animal models of depression. It also has a fast metabolic turnover rate, with a half life of 3 hours in humans. This rapid "hit–and–go" temporal profile suggests that ketamine is likely to act on a system that has ongoing activity with open NMDAR channels. The lateral habenula(LHb) has recently emerged in the coding of negative emotion and pathophysiology of major depression. LHb hosts primarily glutamatergic neurons, but it inhibits brain´s reward centers(including the dopaminergic vental tegmental area(VTA) and the serotonergic dorsal raphe nucleus(DRN), whose hypoactivity has been implicated in depression) either through relay at the GABAergic rostromedial tegmental nucleus(RMTg) or local interneurons within VTA and DRN. Although accumulating evidence suggest that aberrantly overactive LHb is crucial to depression, it remains unknown how the spike patterns of LHb neurons are altered during depressive state and what role it may play in depression etiology and the fast antidepressant effects of ketamine. In this talk, I will present data to show how ketamine regulates mood and depression by blocking the burst firing of LHb. I will also discuss a perisomatic K⁺ buffering mechanism by which neuron–glia interaction regulates LHb burst firing in depression.