The Role of Corticostriatal Microcircuitry in Sensorimotor Integration

皮质纹状体微电路在感觉运动整合中的作用

• 批准号: 10677860
• 负责人: Branden Dennis Sanabria
• 金额: $ 4.13万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10677860
• 关键词: 3-Dimensional; Anatomy; Area; Automobile Driving; Basal Ganglia; Behavior; Behavioral; Brain; Calcium; Cell Nucleus; Cells; Chronic; Communities; Corpus striatum structure; Critical Thinking; Data; Decision Making; Dedications; Discrimination; Disease; Dorsal; Electrophysiology (science); Environment; Esthesia; Fellowship; Foundations; Gilles de la Tourette syndrome; Goals; Histology; Huntington Disease; Image; Image Analysis; Interneurons; Investigation; Lateral; Learning; Maps; Mission; Motor; Movement; Mus; N-Methyl-D-Aspartate Receptors; Neuroanatomy; Neurons; Neurosciences; Parkinson Disease; Parvalbumins; Population; Principal Investigator; Process; Rewards; Role; Sensory; Slice; Structure; Synapses; Synaptic Transmission; Synaptic plasticity; Texture; Training; United States National Institutes of Health; Vibrissae; Viral; Viral Vector; Work; autism spectrum disorder; awake; career; cell type; cellular imaging; confocal imaging; experience; in vivo; in vivo imaging; insight; motor learning; nerve supply; neural; neurophysiology; novel; optogenetics; patch clamp; reconstruction; response; sensory integration; sensory stimulus; skills; somatosensory; two-photon

Project Summary The processing of sensory stimuli is fundamental for the selection of appropriate actions during behavior and learning, a process known as sensorimotor integration. The striatum, a key input center of the basal ganglia, is involved in sensorimotor integration, and disruptions in striatal networks can lead to disorders such as Parkinson’s, Huntington’s, Tourette’s syndrome, and autism spectrum disorder (ASD). In mice, sensations and movements are represented in the brain by changes in neuronal activity in the primary sensory (S1) and motor (M1) cortex respectively. Although S1 and M1 share overlapping projections to the dorsolateral striatum (DLS), which has been heavily implicated in the formation of sensorimotor associations, the underlying circuit dynamics of how activity from S1 and M1 is represented in the DLS during sensory-guided decision making is poorly understood. Recent work in our lab has demonstrated that during a whisker-based sensorimotor integration task, stimulation of M1 corticostriatal projections excites striatal spiny projection neurons (SPNs) and fast spiking interneurons (FSIs) equally, and promotes behavioral responding to the task. In contrast, S1 corticostriatal stimulation produces stronger excitation of FSIs compared to SPNs, and suppresses behavioral responding. These findings strongly suggest that the opposing effects of M1 and S1 corticostriatal stimulation on sensory guided decision-making are due to differences in their connectivity to DLS SPNs and FSIs. This proposal investigates the hypothesis that S1 and M1 corticostriatal projections facilitate sensorimotor integration through differences in their connectivity to SPNs and FSIs in the DLS. A viral circuit mapping strategy along with single- cell filling will be employed in aim 1 to determine the input anatomy of S1 and M1 onto DLS SPNs and FSIs. The capacity for plasticity at these synapses will be assessed in aim 2 using a combination of optogenetic stimulation and electrophysiology. The encoding of sensory and motor related features of a Go/NoGo whisker-based decision-making task in DLS SPNs and FSIs will be assessed in aim 3 using chronic in-vivo 2-photon calcium imaging. This proposed fellowship will support a training environment that is in line with the goals of diversity in the NIH. It provides excellent opportunities to utilize impactful professional relationships both inside and outside the scientific community. Furthermore, it will provides technical training for a strong foundation in neuroanatomy, neurophysiology, and in-vivo imaging. Together, the proposal herein has significant potential to prepare one for a successful scientific career, as well as significantly impact our understanding of sensorimotor integration in the striatum.

项目摘要 感官刺激的处理是行为过程中选择适当动作的基础， 学习，一个被称为感觉运动整合的过程。纹状体是基底神经节的关键输入中心， 参与感觉运动整合，纹状体网络的中断可导致疾病， 帕金森氏症、亨廷顿氏症、图雷特氏综合症和自闭症谱系障碍（ASD）。在小鼠中，感觉和 运动在大脑中通过初级感觉（S1）和运动神经元活动的变化来表示。 (M1)皮质分别。虽然S1和M1共享到背外侧纹状体（DLS）的重叠投射， 它与感觉运动联系的形成有很大关系， 在感觉引导的决策过程中，S1和M1的活动在DLS中的表现方式很差， 明白我们实验室最近的工作表明，在基于胡须的感觉运动整合过程中， 任务，刺激M1皮质纹状体投射兴奋纹状体棘状投射神经元（SPN）和快速 同样地发放中间神经元（FSI），并促进对任务的行为反应。相比之下，S1 与SPN相比，皮质纹状体刺激产生更强的FSI兴奋，并抑制行为 响应.这些发现强烈提示M1和S1皮质纹状体刺激的相反作用， 感觉引导的决策是由于它们与DLS SPN和FSI的连接性的差异。这项建议 研究了S1和M1皮质纹状体投射通过以下方式促进感觉运动整合的假设： 它们与DLS中的SPN和FSI的连接性的差异。一种病毒电路映射策略沿着与单- 在aim 1中将采用单元填充来确定S1和M1到DLS SPN和FSI上的输入解剖结构。的 在这些突触处的可塑性能力将在aim 2中使用光遗传学刺激的组合来评估。 和电生理学。基于Go/NoGo须的感觉和运动相关特征的编码 将在目标3中使用慢性体内双光子钙评估DLS SPN和FSI的决策任务 显像 这项拟议的研究金将支持一个符合非洲多样性目标的培训环境， 国家卫生研究院它提供了极好的机会，利用内部和外部有影响力的专业关系， 在科学界之外。此外，它还将提供技术培训，为以下方面奠定坚实的基础： 神经解剖学、神经生理学和体内成像。总之，本文中的建议具有重大潜力， 为成功的科学生涯做好准备，并显著影响我们对感觉运动的理解 在纹状体中的整合。