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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要感觉刺激的处理对于在行为和行为过程中选择适当的动作至关重要。学习，一个称为感觉运动整合的过程，是基底神经节的关键输入中心。参与感觉运动整合，纹状体网络的破坏可能导致以下疾病：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) 在小鼠中的感觉和功能。大脑中的运动通过初级感觉 (S1) 和运动神经活动的变化来表示 (M1) 皮层虽然 S1 和 M1 都有重叠的背外侧纹状体 (DLS) 投影，这与感觉运动关联的形成、潜在的电路动力学有很大关系在感觉引导决策过程中，S1 和 M1 的活动如何在 DLS 中表示的情况很差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。任务中，刺激 M1 皮质纹状体投射会兴奋纹状体棘投射神经元 (SPN) 并快速相比之下，S1 会平等地刺激中间神经元 (FSI)，并促进对任务的行为反应。与 SPN 相比，皮质纹状体刺激会产生更强的 FSI 兴奋，并抑制行为这些发现强烈表明 M1 和 S1 皮质纹状体刺激对神经元的影响相反。感觉引导决策是由于它们与 DLS SPN 和 FSI 的连接性不同而产生的。研究了 S1 和 M1 皮质纹状体投射通过促进感觉运动整合的假设它们与 DLS 中 SPN 和 FSI 的连接存在差异目标 1 中将采用单元填充来确定 S1 和 M1 在 DLS SPN 和 FSI 上的输入结构。这些突触的可塑性能力将在目标 2 中结合光遗传学刺激进行评估基于 Go/NoGo 胡须的感觉和运动相关特征的编码。 DLS SPN 和 FSI 中的决策任务将在目标 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符合多元化目标的培训环境 NIH 提供了利用内部和外部有影响力的专业关系的绝佳机会。此外，它将提供技术培训，为科学界奠定坚实的基础。神经解剖学、神经生理学和体内成像一起，本文的提议具有巨大的潜力。为成功的科学事业做好准备，并对我们对感觉运动的理解产生重大影响纹状体的整合。