Neural Mechanisms of Tactile Sensation in Rodent Somatosensory Cortex

啮齿动物体感皮层触觉的神经机制

• 批准号: 8023832
• 负责人: Daniel Feldman
• 金额: $ 28.43万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8023832
• 关键词: Action Potentials; Address; Animals; Area; Autistic Disorder; Behavior; Behavioral; Biological Models; Brain; Cells; Cerebral cortex; Code; Complex; Cues; Data; Defect; Detection; Discrimination; Disease; Disease model; Epilepsy; Esthesia; Fire - disasters; Fragile X Syndrome; Frequencies; Gold; Human; Kinetics; Knowledge; Light; Mammals; Measures; Mechanics; Mental Retardation; Modeling; Motion; Nature; Neurobiology; Neurons; Pattern; Perception; Performance; Population; Primates; Process; Property; Protocols documentation; Psychometrics; Psychophysiology; Rattus; Relative (related person); Research; Rodent; Rodent Model; Scanning; Sensory; Sensory Process; Series; Signal Transduction; Somatosensory Cortex; Speed; Surface; Surface Properties; Synapses; System; Tactile; Techniques; Testing; Texture; Time; Touch sensation; Training; Vibrissae; Work; awake; base; computerized data processing; in vivo; information processing; nervous system disorder; neuromechanism; public health relevance; relating to nervous system; sensor; sensory cortex; sensory discrimination; theories; vibration

DESCRIPTION (provided by applicant): How the brain's cerebral cortex functions, and how this function goes awry in diseases like autism and mental retardation, remain unknown. A powerful model system to investigate cortical function is the whisker somatosensory cortex (S1) of rodents. Rodent S1 is a canonical primary sensory area whose cellular and circuit properties are known in remarkable detail, but how these circuits process sensory information is unknown. We propose to investigate how S1 encodes and processes sensory information, which is a critical step to developing an integrated, cellular-to- systems level understanding of cortical function. The resulting description of normal sensory cortical function will help identify the processing defects in autism, mental retardation, and other neurological disorders. To study sensory processing, we focus on sensation of surface texture, which is a basic component of tactile sensation. We will study quantitatively how surface texture is transformed into a pattern of vibrations by the sensory periphery (the whiskers, which function similarly to human fingertips), and encoded by action potentials in populations of neurons in S1. We use the gold-standard technique of quantitatively comparing psychometric, neurometric, and whisker kinetic-based sensory discrimination functions to identify potential sensory codes for texture. In addition, we use modern optogenetics techniques to activate cortical neurons using light, which allows us to perturb neural activity in S1 and determine how different features of cortical spike trains provide sensory information to the animal. Together, these studies will identify the physical and neurobiological signals that convey information about surface texture in somatosensory cortex. This work will contribute to understanding the nature of cortical information processing, and how it is implemented by specific neurons, circuits, and synapses in S1. Conservation of primary sensory cortical function across mammals suggests that principles of sensory processing identified here will be relevant to the human brain. Because rodent S1 is a major disease model for Fragile X mental retardation, epilepsy and other disorders, our work could help establish how these diseases impair cortical function. This work may be particularly relevant for autism, which involves deficits in vibrotactile processing, and whose circuit basis may be revealed by studying defects in S1 processing in rodent models. PUBLIC HEALTH RELEVANCE: This research will identify how the cerebral cortex encodes and processes tactile (touch) inputs, using a rodent model system. Such baseline knowledge about normal cerebral cortex function is critically needed to understand cortical processing defects in autism, mental retardation, and other neurological diseases.

描述（由申请人提供）：大脑的大脑皮层功能以及该功能在自闭症和智力低下等疾病中的差异仍然未知。研究皮质功能的强大模型系统是啮齿动物的晶须体感皮质（S1）。啮齿动物S1是一个规范的主要感官区域，其细胞和电路性能详细地知道，但这些电路如何处理感官信息是未知的。我们建议研究S1如何编码和处理感官信息，这是开发对皮质功能的集成，细胞到系统级别理解的关键步骤。正常感觉皮质功能的结果描述将有助于确定自闭症，智力低下和其他神经系统疾病的处理缺陷。 为了研究感觉处理，我们专注于表面纹理的感觉，这是触觉感觉的基本组成部分。我们将定量研究表面纹理如何通过感觉外围（与人指尖相似的晶须作用）转化为振动模式，并根据S1中神经元种群的动作电位编码。我们使用定量比较心理测量，神经测定和基于晶须动力学的感觉歧视功能的金标准技术来识别潜在的纹理感觉代码。此外，我们使用现代光遗传学技术使用光激活皮质神经元，这使我们能够在S1中扰动神经活动，并确定皮质尖峰列车的不同特征如何为动物提供感官信息。总之，这些研究将确定物理和神经生物学信号，这些信号传达有关体感皮质中表面纹理的信息。 这项工作将有助于理解皮质信息处理的性质，以及如何通过S1中特定的神经元，电路和突触实施。跨哺乳动物的主要感觉皮质功能的保护表明，此处确定的感觉处理原理与人脑有关。由于啮齿动物S1是脆弱X智力迟缓，癫痫和其他疾病的主要疾病模型，因此我们的工作可以帮助确定这些疾病如何损害皮质功能。这项工作可能与自闭症特别相关，自闭症涉及静脉疾病处理的缺陷，并且可以通过研究啮齿动物模型中S1处理中的缺陷来揭示其电路基础。 公共卫生相关性：这项研究将确定大脑皮层如何使用啮齿动物模型系统编码和过程触觉（触摸）输入。对于正常的大脑皮层功能的基线知识至关重要，以了解自闭症，智力低下和其他神经系统疾病的皮质加工缺陷。