CORTICAL SYNAPSES AND CIRCUITS

描述（由申请人提供）：新皮层的多方面能力来自其复杂的细胞成分，特别是在错综复杂的组织回路中运行的异常多样化的中间神经元。多年来，许多研究人员主要使用双重或三重全细胞记录来检查不完整回路中的一两个中间神经元，这些中间神经元通常是模糊不清的。因此，大多数研究人员都被他们的结果之间的差异所淹没，就像“三个盲人和一只大象”的故事一样，并开始相信皮层至少由几十种不同类型的中间神经元组成，这些中间神经元因此必须形成复杂的皮层抑制网络。 在这项应用中，我们计划开发一种稳定的同时八元组全细胞记录技术，直接记录和比较完整皮层抑制回路中的多个解剖学上识别的中间神经元（以更完整地了解大象）。基于我们的初步数据，我们建议测试是否皮质中间神经元可以被分类为少数群体的基础上，他们的轴突分支，以及这些中间神经元是否在功能上不同的角色列（目标1），层（目标2）和/或亚细胞域（目标3）特定的电路。我们的中心假设是，皮层神经元间网络是由九种一般类型的中间神经元，并组织以下三个基本规则。这个项目的发现将支持这些令人惊讶的简单的皮层中间神经元分类方案和电路组织原则。由于改变的中间神经元功能是一种常见的机制，有助于各种神经系统疾病，包括自闭症，癫痫，抑郁症，亨廷顿氏病，神经纤维瘤病，精神分裂症，妥瑞氏综合征和创伤，这个项目也将有助于建立基础，为未来的识别特定的中间神经元类型（S）和/或电路（S）在这些神经系统疾病的每一个改变。

DESCRIPTION (provided by applicant): The multifaceted capability of neocortex emerges from its complicated cellular constituents, particularly the exceptionally diverse interneurons operating in an intricately organized circuit. Over the years many researchers have used primarily dual or triple whole-cell recordings to examine one or two, often ambiguously identified interneurons in incomplete circuits. As a consequence, most researchers have been overwhelmed by the differences between their results, much like the tale of "three blind men and an elephant," and have come to believe that the cortex consists of at least a few dozen of distinct types of interneurons and these interneurons must thus form a sophisticated cortical inhibitory network. In this application, we plan to develop a stable simultaneous octuple whole-cell recording technology to directly record and compare multiple anatomically identified interneurons in complete cortical inhibitory circuits (to see a more complete picture of the elephant). Based on our preliminary data, we propose to test whether cortical interneurons may be classified into a handful of groups based on their axonal arborization, and whether these interneurons serve functionally different roles in column- (aim 1), laminar- (aim 2) and/or subcellular domain (aim 3)-specific circuits. Our central hypothesis is that the cortical interneuronal network is constituted by nine general types of interneurons and is organized following three elemental rules. The findings from this project will support these surprisingly simple cortical interneuron classification scheme and circuit organizational principles. Because altered interneuronal function is a common mechanism contributing to various neurological disorders, including autisms, epilepsy, depression, Huntington's disease, neurofibromatosis, schizophrenia, Tourette's syndrome and trauma, this project will also help to build the groundwork for future identification of specific interneuron type(s) and/or circuit(s) altered in each of these neurological diseases.