Neural Mechanisms of Tactile Sensation in Rodent Somatosensory Cortex

描述（由申请人提供）：大脑的大脑皮层是如何运作的，以及这种功能在自闭症和智力迟钝等疾病中是如何出错的，仍然是未知的。啮齿类动物的须状体感皮层（S1）是研究皮层功能的一个强大的模型系统。啮齿动物S1是一个典型的初级感觉区，其细胞和回路特性非常详细，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，这是一个关键的一步，发展一个综合的，细胞到系统水平的理解皮层功能。对正常感觉皮层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系统疾病的处理缺陷。 为了研究感觉加工，我们集中在表面纹理的感觉，这是触觉的基本组成部分。我们将定量研究表面纹理如何通过感觉外围（胡须，其功能类似于人类指尖）转化为振动模式，并由S1神经元群体中的动作电位编码。我们使用的黄金标准技术，定量比较心理，神经，和胡须动力学为基础的感觉歧视功能，以确定潜在的感觉代码的纹理。此外，我们使用现代光遗传学技术用光激活皮层神经元，这使我们能够干扰S1的神经活动，并确定皮层尖峰序列的不同特征如何为动物提供感觉信息。总之，这些研究将确定物理和神经生物学信号，传达有关表面纹理的信息，在体感皮层。 这项工作将有助于理解皮层信息处理的本质，以及它是如何由特定的神经元，电路和突触在S1。哺乳动物初级感觉皮层功能的保存表明，这里确定的感觉处理原则将与人类大脑有关。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，我们的工作可以帮助确定这些疾病如何损害皮质功能。这项工作可能是特别相关的自闭症，其中涉及缺陷的振动触觉处理，其电路的基础可能会通过研究缺陷S1处理啮齿动物模型。 公共卫生相关性：这项研究将确定大脑皮层如何编码和处理触觉（触摸）输入，使用啮齿动物模型系统。这些关于正常大脑皮层功能的基本知识对于理解自闭症、智力迟钝和其他神经系统疾病中的皮层处理缺陷至关重要。

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.