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: 10314666
• 负责人: Branden Dennis Sanabria
• 金额: $ 3.96万
• 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/10314666
• 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; Discrimination; Disease; Dorsal; Due Process; Electrophysiology (science); Environment; Esthesia; Fellowship; Foundations; Gilles de la Tourette syndrome; Goals; Histology; Huntington Disease; Image; Image Analysis; Interneurons; Investigation; Lateral; Lead; Learning; Mission; Motor; Movement; Mus; N-Methyl-D-Aspartate Receptors; Neuroanatomy; Neurons; Neurosciences; Parkinson Disease; Parvalbumins; Play; 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; base; career; cell type; cellular imaging; confocal imaging; experience; in vivo; in vivo imaging; insight; motor learning; nerve supply; neurophysiology; novel; optogenetics; patch clamp; reconstruction; relating to nervous system; response; 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.

项目总结