Synaptic Circuit Organization of Motor Cortex

运动皮层的突触电路组织

• 批准号: 10451517
• 负责人: Gordon M Shepherd
• 金额: $ 43.16万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10451517
• 关键词: Accounting; Activities of Daily Living; Address; Architecture; Area; Behavior; Brain; Cell Nucleus; Cells; Cervical spinal cord structure; Communication; Complex; Disease; Electrophysiology (science); Epilepsy; Feedback; Forelimb; Grant; Hand; Health; Impairment; Knowledge; Label; Lateral; Link; Liquid substance; Mediating; Methods; Mission; Modeling; Motor; Motor Cortex; Movement; Movement Disorders; Mus; National Institute of Neurological Disorders and Stroke; Neocortex; Neurons; Output; Paralysed; Parents; Pathologic Processes; Pathology; Pathway interactions; Pattern; Public Health; Recurrence; Research; Sensorimotor functions; Sensory; Series; Services; Signal Transduction; Somatosensory Cortex; Source; Spinal Cord; Synapses; System; Tactile; Testing; Thalamic structure; Touch sensation; United States National Institutes of Health; Volition; Work; active duty; arm movement; cell type; disability; experimental study; improved; in vivo; innovation; mental function; motor behavior; neural circuit; neuropathology; optogenetics; programs; somatosensory; systems research; voluntary movement disorder

PROJECT SUMMARY Sensory-guided movements of the arms and hands are essential for many activities of daily living. Pathological processes that impair the cortical circuits mediating these behaviors are a common cause of disability. To better understand and treat these disorders, it will be important to understand the cellular mechanisms in these circuits. Our progress in the previous grant period has helped to elucidate many aspects of the circuit organization of primary motor cortex (M1) neurons in the forelimb area of mouse neocortex. However, a fundamental question remains poorly understood: how are forelimb M1 neurons integrated into functional synaptic circuits with the cells and circuits of primary somatosensory cortex (S1)? This is important to determine, because while the critical importance of somatosensation in controlling movements is well established, the circuits mediating sensorimotor integration in this system are not well characterized. Our working hypothesis is that the forelimb S1—M1 circuit is configured by the cell-type-specific connections of its cortical and thalamic projection neurons to support feedforward somatosensory→motor signaling along complex yet highly specific polysynaptic pathways, leading to excitation of corticospinal neurons. Defining the cellular components of this transcortical loop would be a major step toward elucidating how tactile information is communicated to and integrated by motor cortex neurons to influence cortical output to the spinal cord, in the service of fluid volitional forelimb movements. We propose a research program to test a series of predictions about the cellular organization of the forelimb S1—M1 circuit. The overall aim is to determine the cellular basis for key long-range excitatory circuit connections that mediate communication between forelimb S1 and M1, and between these areas and somatosensory and motor nuclei in the thalamus, particularly the ventral posterior, posterior, and ventrolateral nuclei. To this end, in vivo labeling and ex vivo optogenetic- electrophysiological methods will be used to systematically delineate the cell-type-specific connections mediating thalamus→cortex (Aim 1), cortex→thalamus (Aim 2), and cortex→cortex (Aim 3) communication in this sensorimotor circuit. Overall, the proposed research program is significant and innovative, we believe, because it will generate basic new information about the cellular/synaptic mechanisms underlying the somatosensory→motor transformations at the level of cell-type-specific circuits of the neocortex and thalamus, and thus about the mechanistic basis for sensorimotor functions of the forelimb.

项目摘要 手臂和手的感官引导运动对于许多日常生活至关重要。病理 损害介导这些行为的皮质电路的过程是残疾的常见原因。到 更好地理解和治疗这些疾病，了解这些疾病很重要 电路。我们在上一个赠款期间的进步有助于阐明巡回赛的许多方面 小鼠新皮层的前肢区域中原代运动皮质（M1）神经元的组织。但是， 基本问题仍然鲜为人知：前肢M1神经元如何整合到功能中 与原代体感皮质（S1）的细胞和电路的突触电路？这对 确定，因为虽然节质在控制运动中的至关重要性是很好的 建立的，在该系统中介导感官积分的电路没有很好地表征。我们的 工作假设是前肢S1-M1电路由其细胞类型的特定连接配置 皮质和丘脑投影神经元支持前馈感感测→沿着运动信号传导 复杂但高度特异性的多突触途径，导致皮质脊髓神经元的兴奋。定义 该跨皮层环的细胞成分将是阐明触觉信息的主要步骤 通过运动皮层神经元传达并集成并整合，以影响皮层输出到脊髓 流体意志前肢运动的服务。我们提出了一项研究计划，以测试一系列 关于前肢S1 -M1电路细胞组织的预测。总体目的是确定 关键的远程兴奋电路连接的细胞基础，介导前肢之间的通信 S1和M1，在这些区域以及丘脑中的体感和运动核之间，尤其是 腹侧，​​后和腹侧核。为此，体内标记和离体光学遗理 - 电生理方法将用于系统地描述细胞类型的连接 介导丘脑→皮层（AIM 1），皮层→丘脑（AIM 2）和皮层→皮层→皮层（AIM 3）交流 该感觉运动电路。总体而言，我们认为，拟议的研究计划具有重要的创新性。 因为它将生成有关蜂窝/突触机制的基本新信息 在新皮层和丘脑的细胞类型特异性电路水平上的体感→运动转化， 因此，关于前肢的感觉运动功能的机械基础。

项目成果

Ephus: multipurpose data acquisition software for neuroscience experiments.

• DOI: 10.3389/fncir.2010.00100
• 发表时间: 2010
• 期刊: Frontiers in neural circuits
• 影响因子: 3.5
• 作者: Suter BA;O'Connor T;Iyer V;Petreanu LT;Hooks BM;Kiritani T;Svoboda K;Shepherd GM
• 通讯作者: Shepherd GM

Manipulation-specific cortical activity as mice handle food.

• DOI: 10.1016/j.cub.2022.09.045
• 发表时间: 2022-11-21
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Barrett, John M;Martin, Megan E;Shepherd, Gordon M G
• 通讯作者: Shepherd, Gordon M G

Circuit mapping by ultraviolet uncaging of glutamate.

• DOI: 10.1101/pdb.prot070664
• 发表时间: 2012-09-01
• 期刊: Cold Spring Harbor protocols
• 作者: Shepherd, Gordon M G

Corrigendum: Scaling of Optogenetically Evoked Signaling in a Higher-Order Corticocortical Pathway in the Anesthetized Mouse.

勘误表：麻醉小鼠高阶皮质通路中光遗传学诱发信号的缩放。

• DOI: 10.3389/fnsys.2018.00050
• 发表时间: 2018
• 期刊: Frontiers in systems neuroscience
• 影响因子: 3
• 作者: Li,Xiaojian;Yamawaki,Naoki;Barrett,JohnM;Körding,KonradP;Shepherd,GordonMG
• 通讯作者: Shepherd,GordonMG

Sublayer-specific microcircuits of corticospinal and corticostriatal neurons in motor cortex.

• DOI: 10.1038/nn.2538
• 发表时间: 2010-06
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Anderson, Charles T.;Sheets, Patrick L.;Kiritani, Taro;Shepherd, Gordon M. G.
• 通讯作者: Shepherd, Gordon M. G.