Cortical Synapses and Circuits

描述(申请人提供)：新皮质的多方面能力来自其复杂的细胞组成，特别是在复杂组织的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或三个全细胞记录来检查一个或两个，通常模糊地识别不完整回路中的中间神经元。因此，大多数研究人员被他们的结果之间的差异所淹没，就像“三个盲人和一头大象”的故事一样，他们开始相信，大脑皮质至少由几十种不同类型的中间神经元组成，这些中间神经元必须因此形成一个复杂的皮质抑制网络。在这项应用中，我们计划开发一种稳定的同时八重全细胞记录技术，直接记录和比较完整皮质抑制回路中多个解剖识别的中间神经元(以查看更完整的大象图景)。基于我们的初步数据，我们建议测试是否可以根据皮质中间神经元的轴突分支将其分为几个组，以及这些中间神经元是否在柱状(Aim 1)、板层(Aim 2)和/或亚细胞域(Aim 3)特异性回路中发挥不同的功能。我们的中心假设是，皮质神经元间网络由九种一般类型的中间神经元组成，并遵循三个基本规则进行组织。这个项目的发现将支持这些令人惊讶的简单的皮质间神经元分类方案和电路组织原则。由于神经元间功能改变是导致各种神经疾病的常见机制，包括自闭症、癫痫、抑郁症、亨廷顿病、神经纤维瘤病、精神分裂症、多发性抽动症和创伤，该项目还将有助于为未来确定在这些神经疾病中改变的特定中间神经元类型(S)和/或回路(S)奠定基础。

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.