Establishing a Comprehensive and Standardized Cell Type Characterization Platform

 描述（由申请人提供）：脑回路是大量神经元的复杂互连网络，具有不同的分子、解剖学和生理学特性。神经元细胞类型是神经回路的基本构建块。为了理解大脑回路中信息处理的原理，有一个系统的 了解其每个组成部分的共同和独特属性-细胞类型，它们如何相互连接，以及它们在电路中的功能。通过对众多电路的研究，人们提出了多种关于不同细胞类型在信号处理中的作用的机制。然而，尽管重要，我们还远远没有全面了解大脑或给定回路中细胞类型的数量和种类。我们确实对每个地区的主要细胞类型有丰富的知识，以及许多特定类型的例子。但在大多数情况下，由于缺乏系统的努力，我们不知道大多数回路的完整细胞类型组成，我们对单个细胞之间的变异和异质性程度知之甚少，无论是在给定类型内还是在不同类型之间。为了解决这个问题，我们建议建立一个全面和标准化的细胞类型表征平台，可以扩大规模，系统地检查整个大脑中任何神经回路中细胞类型成分的特性和功能。为了实现这一点，我们提出了一个学术实验室/中心和艾伦研究所之间的合作模型，用于表征特定脑回路中的细胞类型，所有通过QC的daa都将进入艾伦研究所细胞类型数据库并公开。我们将测试一系列实验方法，包括分子，解剖和生理测量及其在单细胞水平上的整合。我们的原理证明研究基于对小鼠大脑中三种主要大脑神经回路的比较：两种密切相关的皮层回路-初级视觉皮层（V1）和初级体感皮层（S1），以及一种更独特的回路-下丘脑/杏仁核情感通路。这两个比较轴在评估我们将测试的细胞类型表征方法的可靠性和通用性方面应该是非常有用的。因此，我们希望确定关键参数和必要的指标，神经元分类到离散的细胞类型，由他们的功能指导。因此，我们预计这个项目及其产生的资源将对研究大脑电路功能和功能障碍的科学界产生广泛的影响和催化作用。

 DESCRIPTION (provided by applicant): The brain circuit is an intricately interconnected network of a vast number of neurons with diverse molecular, anatomical and physiological properties. Neuronal cell types are fundamental building blocks of neural circuits. To understand the principles of information processing in the brain circuit, it is essential to have a systematic understanding of the common and unique properties for each of its components - the cell types, how they are connected to each other, and what are their functions in the circuit. From the study of numerous circuits, many types of mechanisms have been proposed regarding the roles of different cell types in signal processing. However, despite of the importance, we are far from a comprehensive understanding of the number and kinds of cell types in the brain or a given circuit. We do have a wealth of knowledge on the major cell types in each region, and many examples of specific types. But for the most part, due to the lack of systematic efforts, we don't know the complete cell type composition of most circuits, and we have very little idea about the degree of variation and heterogeneity among single cells, both within a given type and between different types. To address this issue, we propose to establish a comprehensive and standardized cell type characterization platform that can be scaled up to systematically examine the properties and function of cell type components in any neural circuits throughout the brain. To implement this, we propose a model for collaboration between academic labs/centers and Allen Institute for characterizing cell types in specific brain circuits, with all the QC-passed daa going into the Allen Institute Cell Types Database and becoming publicly available. We will test a range of experimental approaches, encompassing molecular, anatomical and physiological measurements and their integration at the single cell level. Our proof of principle studies are based on comparison of three major brain neural circuits in the mouse brain: two closely related cortical circuits - primary visual cortex (V1) and primary somatosensory cortex (S1), and a more distinct circuit - the hypothalamus/amygdala emotional pathway. These two axes of comparison should be very informative in assessing the reliability and generality of the cell type characterization approaches we will be testing. We thereby hope to determine the critical parameters and metrics necessary to classify neurons into discrete cell types, guided by their functions. Thus, we anticipate that this project and the resources it produces will have a broad impact and catalytic effect on the scientific community studying brain circuitry function and dysfunction.