Neural Mechanisms of Tactile Sensation in Rodent Somatosensory Cortex

描述(申请人提供)：大脑的大脑皮层是如何运作的，以及在自闭症和智力低下等疾病中这一功能是如何出错的，目前尚不清楚。研究皮质功能的一个强大的模型系统是啮齿类动物的胡须体感皮质(S1)。啮齿动物S1是一个典型的初级感觉区域，其细胞和回路特性已知的非常详细，但这些回路如何处理感觉信息尚不清楚。我们建议研究S1如何编码和处理感觉信息，这是发展对皮质功能的集成的、细胞到系统水平的理解的关键一步。由此得到的对正常感觉皮质功能的描述将有助于识别自闭症、精神发育迟滞和其他神经障碍的加工缺陷。为了研究感觉加工，我们重点研究了表面纹理的感觉，这是触觉感觉的一个基本组成部分。我们将定量研究表面纹理如何通过感觉外周(其功能类似于人类指尖的胡须)转换为振动模式，并由S1神经元群体中的动作电位编码。我们使用定量比较心理测量、神经测量和胡须运动的感觉辨别功能的黄金标准技术来识别潜在的纹理感觉编码。此外，我们使用现代光遗传学技术用光激活皮质神经元，这使我们能够扰乱S1的神经活动，并确定皮质棘波序列的不同功能如何向动物提供感觉信息。总而言之，这些研究将确定传达体感皮质表面纹理信息的物理和神经生物信号。这项工作将有助于理解皮质信息处理的本质，以及它是如何由S1中特定的神经元、回路和突触实现的。哺乳动物初级感觉皮质功能的保守性表明，这里确定的感觉处理原理将与人脑相关。由于啮齿动物S1是脆性X智力低下、癫痫和其他疾病的主要疾病模型，我们的工作可能有助于确定这些疾病是如何损害皮质功能的。这项工作可能对自闭症特别相关，自闭症涉及振动触觉处理的缺陷，其电路基础可以通过研究啮齿动物模型中S1处理的缺陷来揭示。 与公共健康相关：这项研究将使用啮齿动物模型系统确定大脑皮层如何编码和处理触觉(触摸)输入。这些关于正常大脑皮质功能的基线知识对于理解自闭症、智力低下和其他神经疾病的皮质处理缺陷是至关重要的。

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.