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

项目摘要 海马体被认为是支持两者空间记忆过程的关键结构 人类和动物一样。其中许多过程，例如在给定环境中进行自我本地化的能力 以及参与目标导向导航被认为依赖于CA1的特定位置激发 海马区锥体神经元称为定位细胞。一种环境的位置，在该环境中， 位置单元格的增加称为其位置场，该场的形成被认为取决于 整合来自上游脑区的空间输入。而体外实验研究表明，CA1 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，关于如何集成这些输入以生成Place像元的空间精度，人们知之甚少 活体内的活动模式。这在很大程度上是由于从以下位置获取电子录音的固有困难 清醒的、行为正常的动物体内的锥体神经元树突，是鉴定啮齿动物体内定位细胞的先决条件。 目前，钙成像是为数不多的可用于探测脑内亚细胞活动的技术之一。 行为不端的动物。因此，这项建议的目的是确定大脑的功能和解剖组织 利用体内双光子钙在主动导航行为中向海马区细胞的突触输入 成像。通过研究作为定位细胞激发基础的突触活动模式，有可能获得 更好地理解单个神经元如何处理完整的与行为相关的信息 大脑。此外，确定树枝晶在正常情况下处理输入的规则将有所帮助 解决输入整合中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.