CORTICAL SYNAPSES AND CIRCUITS

描述（由申请人提供）：新皮层的多面能力来自其复杂的细胞成分，特别是在复杂组织回路中运作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全细胞记录来检查不完整电路中一个或两个经常被模糊识别的中间神经元。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，并且开始相信皮层至少由几十种不同类型的中间神经元组成，因此这些中间神经元必须形成一个复杂的皮层抑制网络。在这个应用中，我们计划开发一种稳定的同时八元全细胞记录技术，直接记录和比较完整皮层抑制回路中多个解剖鉴定的中间神经元（以看到更完整的大象图像）。基于我们的初步数据，我们建议测试皮层中间神经元是否可以根据它们的轴突树突划分为少数组，以及这些中间神经元是否在柱状（目的1）、层状（目的2）和/或亚细胞结构域（目的3）特异性回路中发挥不同的功能作用。我们的中心假设是皮层间神经元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组织。这个项目的发现将支持这些令人惊讶的简单皮层中间神经元分类方案和电路组织原则。由于神经元间功能的改变是导致各种神经系统疾病的共同机制，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、图雷特综合征和创伤，该项目也将有助于为未来识别这些神经系统疾病中特定的中间神经元类型和/或回路改变奠定基础。

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.