The Functional Significance of Hippocampal Sprouting

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DESCRIPTION (provided by applicant): Axonal sprouting has been proposed to contribute to the mis-wiring of neural circuitry leading to mental illnesses such as schizophrenia or bipolar disorder. The possibility exists that hippocampal formation sprouting may contribute to some of the behavioral symptoms associated with schizophrenia. Unfortunately, little is presently known about the functional 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 (EC) 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 (i.e., two-stage) 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, remain to be fully explored. Here we propose to explore the possibility that manipulating the length of the interval between the first- and second-stage of the progressive lesion may differentially promote the ability of the CTD to support the induction of long-term potentiation. 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. Relevance: More than 2 million Americans suffer from schizophrenia, which is a serious and debilitating form of mental illness. The proposed project will explore whether changes in brain cell connectivity may contribute to some of the behavioral alterations that are associated with schizophrenia.