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Hippocampal Functional Organization

海马功能组织

基本信息

批准号：
7175435
负责人：
CONSTANTINE PAVLIDES
金额：
$ 28.63万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-12-03 至 2009-11-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The hippocampus is one of the most studied brain structures and a great deal is known about its anatomy, physiology and function. Yet, practically nothing is known about its functional organization. A breakthrough in understanding hippocampal function was the discovery of 'place cells'. That is, the majority of hippocampal complex spike cells fire in relation to an animal's position in space, leading to the hypothesis that the hippocampus acts as a 'spatial map'. Other evidence, however, suggests that the hippocampus also participates in non-spatial learning and memory. With regards to neuronal functional organization, two models have been proposed. The first suggests that the hippocampus is organized in a massively parallel distributed network, whereby individual neurons are dispersed throughout the network. The second model proposes that functional organization within the hippocampus follows similar principles as have been observed for primary sensory cortex, namely, a columnar organization. Although there is evidence supporting both views, these have created even more controversy. One problem has been that using traditional electrophysiological recording techniques, it is difficult to determine how the map may be arranged, since only a few neurons can be recorded simultaneously. In preliminary studies, we used a combination of behavioral, immunocytochemical (ICC) and electrophysiological recordings to detect neuronal activation within the hippocampus and thus determine functional organization. We minimized the animal's sensory stimuli for 48h, by placing them in a dark enclosure. We then exposed them briefly to an environment with visual spatial cues and using the immediate-early gene zif-268 as a marker of neuronal activity we found 'clusters' of zif-268 immunoreactive (IR) cells, in animals restricted to a specific part of space. Combined ICC/electrophysiological recordings revealed that the zif-268 IR cells correspond to place cells. Further, we observed that NMDAR antagonists, which have previously been shown to disrupt place cells also, disrupt the zif-268 IR clusters. In the proposed studies, we will map the entire hippocampus in terms of neuronal functional organization for space. We will then attempt to determine how the cells within a cluster may function and the types of interactions which may occur between the clusters. Finally, we will investigate whether a similar functional neuronal organization occurs in animals engaged in non-spatial memory tasks

描述（由申请人提供）：海马体是研究最多的大脑结构之一，关于其解剖学，生理学和功能有很多已知的。然而，实际上对其功能组织一无所知。理解海马功能的一个突破是“定位细胞”的发现。也就是说，大多数海马复合体棘细胞的放电与动物在空间中的位置有关，这导致了海马作为“空间地图”的假设。然而，其他证据表明海马体也参与非空间学习和记忆。关于神经元的功能组织，已经提出了两种模型。第一种观点认为海马体是以一个大规模并行分布的网络组织起来的，单个神经元分散在整个网络中。第二个模型提出，海马内的功能组织遵循与初级感觉皮层相似的原则，即柱状组织。虽然有证据支持这两种观点，但这些观点引起了更多的争议。一个问题是，使用传统的电生理记录技术，很难确定如何安排地图，因为只有少数神经元可以同时记录。在初步研究中，我们使用了行为，免疫细胞化学（ICC）和电生理记录的组合来检测海马内的神经元激活，从而确定功能组织。我们将动物置于黑暗的围栏中，使其感官刺激最小化48小时。然后，我们将它们短暂地暴露在具有视觉空间线索的环境中，并使用立即早期基因zif-268作为神经元活动的标记，我们发现了zif-268免疫反应（IR）细胞的“集群”，这些细胞在动物中被限制在空间的特定部分。结合ICC/电生理记录显示，zif-268 IR细胞对应于位置细胞。此外，我们观察到，NMDAR拮抗剂，其先前已显示破坏定位细胞，也破坏zif-268 IR簇。在拟议的研究中，我们将绘制整个海马体的神经元功能组织的空间。然后，我们将尝试确定集群内的细胞如何发挥作用，以及集群之间可能发生的相互作用的类型。最后，我们将研究在从事非空间记忆任务的动物中是否也会出现类似的功能性神经元组织