Cortical circuit mechanisms of sensorimotor object localization

感觉运动物体定位的皮层回路机制

• 批准号: 10054205
• 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
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-11-15 至 2022-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054205
• 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

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 感觉和运动信号如何在大脑中整合以产生物体位置的感知仍然存在 不太了解。初级躯体感觉皮层（S1）是感觉运动整合的候选部位， 是对象定位的基础。鼠标S1是一个强大的系统，在其中发现一般原则， 感觉运动整合的特定电路实现，即物体位置的形状感知。揭示 这些将提供健康皮层功能的基本知识， 中风、脊髓损伤和其他神经系统疾病可能会得到更充分的了解。 这项工作的长期目标是了解触觉的细胞和电路机制 perception.该建议的重点是S1如何在主动触摸过程中整合感觉和运动信号 行为。头部固定的小鼠可以通过主动探索来确定物体的角度位置， 胡须复杂的神经处理是这种简单行为的基础，这使它成为一个优秀的模型 用于解剖躯体感觉整合的电路机制的系统。存在几种竞争模型， 大脑是如何完成这项任务的它们在感觉运动信号的类型、来源和整合位置上存在差异 采用区分这些模型对于理解内部运动信号在 皮层回路在触觉感知的构建中起作用。以前的研究未能做到这一点，因为限制， 任务设计和行为变异量化。该提案克服了这些限制， 创新的方法，包括改进的定位任务，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。 该提案的总体目标是通过以下方式区分感觉运动整合模型： 量化行为，识别S1中对象定位的候选代码，这些代码是如何构造的，以及它们的 影响感知。我们的中心假设是，物体的位置是由一组兴奋性的 在S1的L5B中，通过触摸激活神经元，并且L5B细胞中的对象位置调谐需要丘脑和 来自S1的L4的输入和减去运动的触摸信号。我们进一步假设M1输入放大L5 B 活动而不影响对象位置调整。我们的初步数据支持这一假设， 细胞类型和层特异性记录在S1和对象定位过程中的光遗传电路操纵。的 假设将通过追求三个具体目标进行测试。1)识别S1中对象位置的候选代码 神经元2)识别有助于S1神经元中对象位置调谐的信号的来源。3)测试对象 具有S1回路的闭环光遗传学操纵的定位模型。提议的捐助 研究将是重要的，因为它将产生有关S1中神经动力学的详细知识， 触摸知觉的基础，揭示感觉运动整合和特定皮层回路的一般原则 在行为期间实现该集成，并将其全部打包到可访问的资源中。