The Role of Corticostriatal Microcircuitry in Sensorimotor Integration

项目摘要 感官刺激的处理是在行为和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紊乱，如 帕金森氏症、亨廷顿氏症、抽动症和自闭症谱系障碍(ASD)。在老鼠身上，感觉和 运动在大脑中表现为初级感觉(S1)和运动中神经元活动的变化 (M1)大脑皮层。虽然S1和M1对背外侧纹状体(DLS)有重叠的投射， 它与感觉运动关联的形成有很大的牵连，这是潜在的电路动力学 在感官引导的决策过程中，来自S1和M1的活动如何在DLS中被表示是很差的 明白了。我们实验室最近的工作表明，在基于晶须的传感器电机集成过程中 任务，刺激M1皮质纹状体投射兴奋纹状体棘突投射神经元(SPN) 刺激中间神经元(FSIS)，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FSIS兴奋，并抑制行为 正在回应。这些发现有力地表明，刺激M1和S1皮质纹状体的相反作用 感觉引导的决策是由于它们与DLS、SPN和FSIS的连接不同。这项建议 研究了S1和M1纹状体投射通过促进感觉运动整合的假说 它们与DLS中的SPN和FSIS的连接性差异。一种病毒式电路映射策略以及单- 在目标1中将使用单元填充来确定S1和M1到DLS SPN和FSIS的输入解剖。这个 这些突触的可塑性能力将在目标2中使用光遗传刺激的组合进行评估。 和电生理学。基于GO/NOGO晶须的感觉和运动相关特征的编码 在目标3中，将使用慢性体内双光子钙来评估DLS SPN和FSIS中的决策任务 成像。 这项拟议的研究金将支持符合#年多样性目标的培训环境。 美国国立卫生研究院。它提供了在内部和外部利用有影响力的职业关系的绝佳机会 在科学界之外。此外，它还将提供技术培训，以巩固 神经解剖学、神经生理学和活体成像。总之，这里的建议有很大的潜力 为成功的科学生涯做好准备，并对我们对感觉运动的理解产生重大影响 纹状体内的整合。

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.