Research on memory and plasticity has focused on the hippocampus for some time. The cortical regions surrounding the hippocampus including the perirhinal, postrhinal, and entorhinal cortices have been appreciated primarily because they provide the major interface between cortical unimodal and polymodal sensory processing regions and the hippocampus. Whereas recent neuroanatomical findings have served to reinforce this view, the results of experimental lesion and electrophysiological studies now indicate that these regions may make unique contributions to memory, in addition to their connectional contributions to hippocampal functions. The rat and the monkey have traditionally provided the primary animal models for memory research, but mice are becoming more widely used, especially since the development of technologies for manipulating the mouse genome. Unfortunately, most of the neuroanatomy and much of the behavior providing the background for neuroscience approaches to memory research using mouse models are based on assumptions drawn from what is known about the rat. In particular, the organization of mouse hippocampal circuitry is largely assumed from findings in the rat. Additionally, spatial tasks commonly used in mice are drawn from a battery of spatial tasks at which rats are known to perform well. Yet, direct behavioral comparisons between laboratory rats and laboratory mice on similar tests of spatial processing ability indicate that there often substantial cross-species differences in performance measures. Available evidence suggests that mice may not perform spatial tasks as well as rats do, and that the discrepancy reflects differences in hippocampal processing of spatial or contextual information. If mice and rats process sensory information for its spatial content differently, this should be evident in the organization of the structures corticohippocampal systems in the two species. The guiding hypothesis of the proposed studies is that mice differ from rats in the processing of spatial information and that the differences are reflected in the functional architecture of corticohippocampal systems. Accordingly, a major objective of the proposed studies is to examine hypotheses about basic connectional principles of the mouse corticocortical and corticohippocampal circuitry. Neuroanatomical studies will be conducted using a mouse strain chosen to provide the best comparison with research conducted in the rat and to complement other ongoing research in the mouse. These experiments will include cytoarchitectonic, histochemical, and tract tracing studies of the hippocampal formation and the cortical regions that surround the hippocampus. Another major aim of the proposed studies is to use neuropsychological approaches within a comparative framework to investigate the function of specific target structures.
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