The Functional Significance of Hippocampal Sprouting

描述(由申请人提供)：在阿尔茨海默病患者的海马结构中，死后观察到神经元发芽。存在这样一种可能性，即海马体回路的重组可能：1)导致与疾病相关的行为症状；或2)补偿投射到海马区的内嗅神经元的损失。不幸的是，目前对中枢神经系统(CNS)发芽的行为意义知之甚少。本小规模研究的目的是评价大鼠单侧损毁内嗅皮层后，海马齿状回发芽的功能意义。这项研究将集中在一期或进行性EC损伤后，增殖的同源输入(即，交叉颞齿投射-CTD)的突触有效性。已知进行性EC损害可加速隔齿、连合/联合和CTD向齿状回萌发，然而，进行性损害对CTD支持长时程增强的能力的影响尚不清楚，长时程增强是突触有效性的一种衡量可能与学习和记忆相关的指标。萌发的CTD通路具有特殊的意义，其原因是：1)CTD通路与正常同侧内嗅觉传入齿状回的同源神经元位于同一细胞层；2)它与单侧内嗅觉损伤后空间记忆的恢复有关。尤其值得注意的是，内嗅区的进行性损害已被证明可以使空间记忆免于与内嗅区损伤相关的典型缺陷。这一电生理分析将为今后评估中枢神经系统发芽的功能意义奠定基础。

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.