Functional architecture of a face processing area in the common marmoset

项目摘要/摘要 在理解社会认知的神经基础方面存在着根本性的差距。关联的非典型行为 精神障碍，如自闭症谱系障碍或严重抑郁障碍，常伴有缺陷 在社交方面。了解这些缺陷并开发有针对性的治疗方法将继续证明 在了解典型社会认知的神经基础之前，这是不可能的。为了揭示这些神经基础，它是 这一提议的中心论点是关注那些允许精确的外部因素的社会认知成分 刺激操作，以阐明社会信息处理。面孔正是形成了这样一种独特的 连接视觉和社会认知的社会刺激。更重要的是，人脸是由一个高度组织的系统处理的 紧密连接成一个面部处理网络的皮质区域。尽管如此，过去对面部贴片的研究 已经严重地局限于单面细胞的特性。为了克服这些限制， 最近发现普通的绒猴面部有表面的斑块，当与 功能性双光子钙成像，能够同时记录大量面部细胞。 长期目标是建立对社会认知的机械性理解。其目的是澄清 一类社会相关的刺激是如何由神经群体以细胞类型依赖的方式编码的。这个 中心假设是，人脸面片包含唯一表示空间组织中的人脸的地图 和细胞类型特定的方式。这一提议的基本原理是，它将建立 面孔，社会认知的基本组成部分，从单细胞水平到新模型中的大脑皮层映射 该系统符合现代基因编辑方法，因此也适用于疾病模型开发。这一假说将 通过追求三个特定目标进行测试：1)确定面部贴片的功能特异性；2)识别 面部贴片内的空间组织原理；以及3)阐明细胞类型对 人脸处理。在第一个和第二个目标下，将使用双光子显微镜来测量神经活动。 从一大群神经元中。这将允许确定人脸的空间组织 申述。在第三个目标下，这项技术将与组织清除和体积测量相结合 免疫组织化学可提供细胞形态和细胞类型的特定信息 神经元。这项提议的方法是创新的，因为它结合了几种尖端技术和 一个新的模型系统，以建立一个关键的社会大脑回路的功能架构。这项研究是 意义重大，因为它产生了对人脸处理的机械性理解，阐明了关键环节 在视觉系统和社会大脑之间，并形成了一个新的模型系统，其中进一步的假设 精神障碍的潜在机制可以经过严格的测试，以获得对 制度对我们理解典型的和非典型的人类行为有明显的贡献。

PROJECT SUMMARY/ABSTRACT There is a fundamental gap in understanding the neural bases of social cognition. Atypical behaviors associated with mental disorders like autism spectrum disorders or major depressive disorder often present with deficits in social interaction. Understanding these deficits and developing targeted therapies will continue to prove impossible until the neural bases of typical social cognition are understood. To reveal these neural bases, it is the central thesis of this proposal to focus on those components of social cognition that allow precise external stimulus manipulation to elucidate social information processing. Faces form just such a category of uniquely social stimuli that bridge vision and social cognition. More so, faces are processed by a highly organized system of cortical areas that are tightly interconnected into a face-processing network. Still, past work on face patches has been critically limited to the properties of single face cells. In order to overcome these limitations, the common marmoset was recently discovered to have superficially located face patches, which, when paired with functional two-photon calcium imaging, enables simultaneous recordings from large populations of face cells. The long-term goal is to establish a mechanistic understanding of social cognition. The objective is to elucidate how a class of socially relevant stimuli is encoded by neural population in a cell-type dependent manner. The central hypothesis is that a face patch contains a map that exclusively represents faces in a spatially organized and cell-type specific manner. The rationale of this proposal is that it will establish the neural representation of faces, a basic component of social cognition, from the level of single cells to cortical maps in a new model system amenable to modern gene-editing approaches and thus disease model development. The hypothesis will be tested by pursing three specific aims: 1) to determine the functional specificity of a face patch; 2) to identify the principles of spatial organization within a face patch; and 3) to elucidate cell-type specific contributions to face processing. Under the first and second aim, two-photon microscopy will be used to measure neural activity from a large population of neurons. This will allow the determination of the spatial organization of face representations. Under the third aim, this technique will be combined with tissue clearing and volumetric immunohistochemistry to contribute morphological and cell type specific information about the population of neurons. The approach of this proposal is innovative because it combines several cutting-edge techniques with a novel model system to establish the functional architecture of a key social brain circuit. This research is significant because it generates a mechanistic understanding of face processing, illuminates a critical link between the visual system and the social brain, and forms a new model system in which further hypotheses underlying mechanisms of mental disorders can be rigorously tested to gain mechanistic understanding of a system tangibly contributing to our understanding of typical and atypical human behavior.