Cortical circuit mechanisms of sensorimotor object localization

感觉运动物体定位的皮层回路机制

基本信息

批准号：
10317072
负责人：
Samuel Andrew Hires
金额：
$ 36.09万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-11-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10317072
关键词：
Affect American Area Behavior Behavioral Biological Models Brain Calcium Cells Code Data Disease Electrophysiology (science)Goals Head Human Image Impairment Individual Inherited Knowledge Location Mammals Mission Modeling Motion Motor Motor Cortex Movement Mus Neurologic Neurons Perception Play Population Positioning Attribute Process Public Health Research Resources Role Sensory Shapes Signal Transduction Site Somatosensory Cortex Speed Spinal Injuries Stroke System Tactile Techniques Technology Testing Thalamic structure Time Touch sensation United States National Institutes of Health Variant Vibrissae Whole-Cell Recordings Work cell type design disability impact excitatory neuron improved inhibitory neuron innovation mental representation mouse model nervous system disorder neural patterning object perception optogenetics post stroke relating to nervous system response seal somatosensory

项目摘要

PROJECT SUMMARY How sensory and motor signals are integrated in the brain to produce perception of object location remains poorly understood. Primary somatosensory cortex (S1) is a candidate site for sensorimotor integration that underlies object localization. Mouse S1 is a powerful system in which to uncover general principles and specific circuit implementations of sensorimotor integration that shape perception of object location. Revealing these will provide fundamental knowledge of healthy cortex function from which processing disruptions from stroke, spinal injury, and other neurological disorders may be more fully understood. The long-term goal of this work is to understand cellular and circuit mechanisms underlying tactile perception. This proposal focuses on how S1 integrates sensory and motor signals during active touch behaviors. Head-fixed mice can determine the angular position of objects by active exploration with a single whisker. Sophisticated neural processing underlies this simple behavior, which makes it an excellent model system for dissecting circuit mechanisms of somatosensory integration. Several competing models exist for how the brain solves this task. They differ in the type, origin, and integration location of sensorimotor signals used. Distinguishing between these models is critical for understanding the role internal motor signals in cortical circuits play in construction of tactile perception. Prior studies failed to do so because of limitations in task design and quantification of behavioral variation. This proposal overcomes these limitations with innovative approaches that include an improved localization task, high-speed sensorimotor tracking, cell type- specific electrophysiology, calcium imaging, sophisticated decoding models, and closed-loop optogenetics. The overall objective of this proposal is to distinguish between sensorimotor integration models by quantifying behavior, identifying candidate codes for object location in S1, how these are constructed, and their influence on perception. Our central hypothesis is that object location is encoded by the set of excitatory neurons activated by touch in L5B of S1, and that object location tuning in L5B cells requires both thalamic input and motion-subtracted touch signals from L4 of S1. We further hypothesize that M1 input amplifies L5B activity without affecting object location tuning. This hypothesis is supported by our preliminary data including cell-type and layer-specific recordings in S1 and optogenetic circuit manipulation during object localization. The hypothesis will be tested by pursuing three Specific Aims. 1) Identify candidate codes for object location in S1 neurons. 2) Identify the origin of signals contributing to object location tuning in S1 neurons. 3) Test object localization models with closed-loop optogenetic manipulation of S1 circuits. The contribution of the proposed research will be significant because it will generate detailed knowledge about the neural dynamics in S1 that underlie touch perception, uncover general principles of sensorimotor integration and specific cortical circuit implementations of that integration during behavior, and package it all into a publically accessible resource.

项目摘要感官和电机信号如何集成在大脑中，以产生对象位置的感知理解不佳。原发性体感皮质（S1）是一个候选感觉运动集成的位点，基础对象本地化。鼠标S1是一个强大的系统，可以揭示一般原则和感觉运动集成的特定电路实现，以形成对象位置的感知。揭示这些将提供有关健康皮层功能的基本知识，从中处理中断中风，脊柱损伤和其他神经系统疾病可能会更充分地理解。这项工作的长期目标是了解触觉基础的细胞和电路机制洞察力。该建议重点介绍S1在主动触摸期间如何整合感官和电机信号行为。头部固定小鼠可以通过单个主动探索来确定物体的角度位置晶须。复杂的神经处理是这种简单行为的基础，这使其成为一个极好的模型解剖体感应整合电路机制的系统。存在几种竞争模型大脑如何解决此任务。它们在感觉运动信号的类型，来源和集成位置不同用过的。区分这些模型对于理解内部电动机信号的作用至关重要皮质电路在触觉感知的建设中发挥作用。先前的研究未能做到这一点行为变化的任务设计和量化。该提案通过创新方法包括改进的本地化任务，高速感觉运动跟踪，细胞类型特定的电生理学，钙成像，复杂的解码模型和闭环光遗传学。该提案的总体目的是通过量化行为，识别候选者在S1中的对象位置，如何构造这些代码及其对感知的影响。我们的中心假设是对象位置是由兴奋性集合编码的 S1的L5B中触摸激活的神经元，在L5B细胞中调谐的对象位置需要两个丘脑来自S1的L4的输入和运动提取的触摸信号。我们进一步假设M1输入放大L5B 不影响对象位置调整的活动。我们的初步数据包括在物体定位期间，S1中的细胞类型和层特异性记录以及光遗传电路操作。这假设将通过追求三个具体目标来检验。 1）确定S1中对象位置的候选代码神经元。 2）确定导致对象位置调整S1神经元中的信号的起源。 3）测试对象 S1电路的闭环光遗传操作的定位模型。提议的贡献研究将是重要的，因为它将对S1中神经动态产生详细的知识基础触摸感知，感觉运动整合的一般原理和特定的皮质回路该集成在行为过程中的实现，并将其全部包装到公开访问的资源中。