The Functional Significance of Hippocampal Sprouting

描述（由申请人提供）：在阿尔茨海默病患者死后的海马形成中观察到神经元发芽。海马体电路的重组可能：1)与疾病相关的行为症状有关；或者2)补偿投射到海马体的内嗅神经元的损失。不幸的是，目前对发芽在中枢神经系统（CNS）中的行为意义知之甚少。本研究旨在探讨大鼠单侧内嗅皮质损伤后海马区齿状回萌发的功能意义。本研究将重点关注一期或进行性EC病变后增殖同源输入（即交叉颞齿投影- CTD）的突触功效。众所周知，进行性EC病变会加速齿状回的隔齿状突起、联合/联合突起和CTD的生长，然而，进行性病变对CTD支持长期增强能力的影响尚不清楚，长期增强是一种可能与学习和记忆相关的突触效能的衡量标准。发芽的CTD通路特别有趣，因为：1)它出现在与正常同侧齿状回的同侧嗅内输入相同的对侧同源细胞层；2)与单侧内嗅损伤后空间记忆的恢复有关。特别值得注意的是，内嗅区域的进行性病变已被证明可以使空间记忆免于通常与内嗅损伤相关的缺陷。这项电生理分析将为进一步研究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.