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 感觉刺激的处理对于在行为过程中选择适当的行动至关重要 学习，一种称为感觉运动集成的过程。纹状体是基底神经节的关键输入中心，是 参与感觉运动集成以及纹状体网络中的破坏会导致疾病，例如 帕金森氏症，亨廷顿，图雷特综合症和自闭症谱系障碍（ASD）。在小鼠中，感觉和 运动在主感觉（S1）和电动机中的神经元活性的变化表示大脑中的运动 （M1）皮质。尽管S1和M1与背外侧纹状体（DLS）共享重叠的项目，但 这很大程度上与感觉运动关联的形成，底层电路动力学 在感觉引导决策过程中，DLS中S1和M1的活动的表现很差 理解。我们实验室的最新工作表明，在基于晶须的感觉运动集成期间 任务，刺激M1皮质纹状体项目激发纹状体棘刺神经元（SPN）和快速 同样尖刺中间神经元（FSIS），并促进对任务的行为反应。相反，S1 与SPN相比 回应。这些发现强烈表明M1和S1皮质纹状体刺激对 感官指导的决策是由于它们与DLS SPN和FSIS的连通性差异所致。这个建议 调查了S1和M1皮质纹状体项目的假设，通过 它们与DLS中SPN和FSI的连通性差异。病毒电路映射策略以及单一 细胞填充将在AIM 1中进行，以确定S1和M1在DLS SPN和FSIS上的输入解剖结构。这 这些突触的可塑性的能力将在AIM 2中使用光遗传学刺激进行评估 和电生理学。 GO/Nogo Whisker的感官和运动相关特征的编码 DLS SPN和FSI中的决策任务将在AIM 3中使用慢性体内2光子钙进行评估 成像。 拟议的奖学金将支持培训环境，该环境符合多样性的目标 NIH。它提供了极好的机会，可以利用内部和内部和 在科学界之外。此外，它将为强大的基础提供技术培训 神经解剖学，神经生理学和体内成像。同时，此处的提议具有很大的潜力 为成功的科学生涯做准备，并显着影响我们对感觉运动的理解 纹状体中的整合。