Dendritic Organization of Synaptic Input to CA1 Hippocampal Place Cells during Spatial Navigation

项目摘要 海马被认为是支持空间记忆过程的关键结构， 人类和动物一样。其中许多过程，例如在给定环境中自我定位的能力， 以及参与目标导向导航被认为取决于CA1的位置特异性激发 海马锥体神经元称为定位细胞。一个环境的位置，在这个位置上， 位置细胞的增加称为其位置场，该场的形成被认为取决于 整合来自上游大脑区域的空间输入。虽然体外实验工作表明，CA 1 海马锥体神经元能够进行被动和主动形式的突触整合， 令人惊讶的是，人们对这些输入是如何整合的，以产生一个位置细胞的空间精确度知之甚少。 体内的活动模式。这在很大程度上是由于获得电子记录的固有困难， 锥体神经元树突在清醒，行为动物，一个先决条件，以确定在啮齿动物的位置细胞。 目前，钙成像作为少数几种可用于探测细胞内亚细胞活性的技术之一存在。 行为动物。因此，本建议的目的是确定的功能和解剖组织的 海马定位细胞主动导航行为中突触输入 显像通过研究作为位置细胞放电基础的突触活动的模式，有可能获得一个 更好地了解单个神经元如何处理完整的行为相关信息， 个脑袋此外，确定树突在正常条件下处理输入的规则将有所帮助 说明输入整合的异常如何导致神经病理疾病。

Project Summary The hippocampus has been identified as a critical structure for supporting spatial memory processes in both humans and animals alike. Many of these processes such as the ability to self-localize in a given environment as well as engage in goal-directed navigation are thought to depend on the location-specific firing of CA1 hippocampal pyramidal neurons called place cells. The position of an environment at which the firing rate of a place cell increases is called its place field and the formation of this field is thought to depend on the integration of spatial inputs from upstream brain regions. While experimental work in vitro has shown that CA1 hippocampal pyramidal neurons are capable of both passive and active forms of synaptic integration, surprisingly little is known about how these inputs are integrated to generate a place cell's spatially precise activity patterns in vivo. This is largely due the inherent difficulty of obtaining electrical recordings from pyramidal neuron dendrites in awake, behaving animals, a prerequisite for identifying place cells in rodents. Currently, calcium imaging exists as one of the few techniques available to probe subcellular activity in the behaving animal. Thus, the aim of this proposal is to determine the functional and anatomical organization of synaptic input to hippocampal place cells during active navigation behavior using in vivo two-photon calcium imaging. By investigating the patterns of synaptic activity which underlie place cell firing, it is possible to gain a greater understanding of the how individual neurons process behaviorally-relevant information in the intact brain. Additionally, determining the rules by which dendrites process input under normal conditions will help address how abnormalities in input integration can result in neuropathological disease.