Hippocampal Functional Organization

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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