Hippocampal Functional Organization

描述（由申请人提供）：海马体是研究最多的大脑结构之一，对其解剖、生理和功能有很多了解。然而，它的功能组织却几乎一无所知。“位置细胞”的发现是了解海马体功能的一个突破。也就是说，大部分海马体复合体刺突细胞的活动与动物在空间中的位置有关，这导致了海马体充当“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，提出了两种模型。第一种观点认为海马体是一个大规模并行分布的网络，单个神经元分散在整个网络中。第二个模型提出，海马体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。尽管有证据支持这两种观点，但这两种观点引发了更多的争议。一个问题是，使用传统的电生理记录技术，很难确定该地图可能是如何排列的，因为只能同时记录几个神经元。在初步研究中，我们结合了行为、免疫细胞化学（ICC）和电生理记录来检测海马内的神经元激活，从而确定功能组织。我们把动物放在一个黑暗的围栏里，在48小时内把它们的感官刺激降到最低。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，并使用即时早期基因zif-268作为神经元活动的标记，我们在被限制在特定空间部分的动物中发现了zif-268免疫反应（IR）细胞的“簇”。结合ICC/电生理记录显示，zif-268 IR细胞与位置细胞相对应。此外，我们观察到NMDAR拮抗剂，先前已被证明可以破坏位置细胞，也会破坏zif-268 IR簇。在拟议的研究中，我们将根据空间的神经元功能组织绘制整个海马体。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存在类似的功能神经元组织

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