The Functional Significance of Hippocampal Sprouting

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DESCRIPTION (provided by applicant): Neuronal sprouting has been observed post-mortem in the hippocampal formation of patients suffering from Alzheimer's disease. The possibility exists that the reorganization of hippocampal circuitry may: 1) contribute to the behavioral symptoms associated with the disease; or 2) compensate for the loss of entorhinal neurons projecting to the hippocampus. Unfortunately, little is presently known about the behavioral significance of sprouting in the central nervous system (CNS). The purpose of this small-scale investigation is to evaluate the functional significance of sprouting in the dentate gyrus of the hippocampal formation after unilateral lesions of the entorhinal cortex in rats. This study will focus on the synaptic efficacy of a proliferated homologous input (i.e., the crossed temporodentate projection -- CTD) after a one-stage or progressive EC lesion. Progressive EC lesions are known to accelerate septodentate, commissural/associational, and CTD sprouting to the dentate gyrus, however, the effects of progressive lesions on the ability of the CTD to support long-term potentiation, a measure of synaptic efficacy that may have relevance to learning and memory, are unknown. The sprouted CTD pathway is of special interest because: 1) it emerges from the same cell layer in the contralateral homologue as the normal ipsilateral entorhinal input to the dentate gyrus; and 2) it has been implicated in the recovery of spatial memory after unilateral entorhinal injury. Particularly noteworthy, progressive lesions of the entorhinal area have been shown to spare spatial memory from the deficits typically associated with entorhinal injury. This electrophysiological analysis will lay the foundation for future work assessing the functional significance of CNS sprouting.