The Functional Significance of Hippocampal Sprouting

海马出芽的功能意义

• 批准号: 7558319
• 负责人: JULIO J RAMIREZ
• 金额: $ 7.79万
• 依托单位: DAVIDSON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7558319
• 关键词: Academic Research Enhancement Awards; Ache; Affect; Applications Grants; Behavioral; Behavioral Symptoms; Bipolar Disorder; Cells; Chemosensitization; Cholinergic Agents; Complex; Contralateral; Deafferentation procedure; Development; Exhibits; Foundations; Funding; Future; Glutamates; Goals; Grant; Hippocampal Formation; Hippocampus (Brain); Homologous Gene; Injury; Investigation; Ipsilateral; Learning; Length; Lesion; Lesion by Stage; Long-Term Potentiation; Measures; Memory; Memory impairment; Mental disorders; National Institute of Mental Health; Nature; Neuraxis; Operative Surgical Procedures; Pathway interactions; Perforant Pathway; Performance; Proliferating; Purpose; Rate; Rattus; Recovery; Research; Schizophrenia; Secondary Lesion; Short-Term Memory; Staging; Study Section; Synapses; Synaptic plasticity; System; Time; Week; Work; abstracting; axonal sprouting; cholinergic; day; dentate gyrus; entorhinal cortex; functional status; granule cell; insight; interest; neural circuit; neural model; neurophysiology; programs; response

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.

描述（由申请人提供）：轴突发芽被认为是导致精神疾病（如精神分裂症或双相情感障碍）的神经回路错误布线的原因。海马结构发芽可能导致与精神分裂症相关的一些行为症状。遗憾的是，目前对中枢神经系统（CNS）中发芽的功能意义知之甚少。本研究旨在探讨内嗅皮层单侧损伤后海马齿状回出芽的功能意义。这项研究将集中在增殖的同源输入的突触功效（即，交叉颞齿突- CTD）在一期或进行性（即，两阶段）EC病变。已知进行性EC病变可加速隔齿、连合/联合和CTD发芽至齿状回。然而，进行性病变对CTD支持长时程增强（一种可能与学习和记忆相关的突触功效的测量）的能力的影响仍有待充分探索。在这里，我们建议探索操纵进展性病变第一阶段和第二阶段之间的间隔长度可能会差异性地促进CTD支持诱导长时程增强的能力的可能性。发芽CTD途径是特别感兴趣的，因为：1）它出现在同一个细胞层在对侧同源作为正常同侧内嗅输入到齿状回;和2）它已经牵连在单侧内嗅损伤后的空间记忆的恢复。特别值得注意的是，进行性病变的内嗅区已被证明是备用的赤字通常与内嗅损伤的空间记忆。这种电生理分析将为今后的工作奠定基础，评估中枢神经系统发芽的功能意义。相关性：超过200万美国人患有精神分裂症，这是一种严重和使人衰弱的精神疾病。拟议的项目将探索脑细胞连接的变化是否可能导致与精神分裂症相关的一些行为改变。

项目成果

The role of axonal sprouting in functional reorganization after CNS injury: lessons from the hippocampal formation.

轴突出芽在中枢神经系统损伤后功能重组中的作用：海马形成的教训。

• 发表时间: 2001
• 期刊: Restorative neurology and neuroscience.
• 作者: Ramirez,JJ

Bilateral entorhinal cortex lesions impair acquisition of delayed spatial alternation in rats.

双侧内嗅皮层损伤损害大鼠延迟空间交替的获得。

• DOI: 10.1016/j.nlm.2006.09.002
• 发表时间: 2007
• 期刊: Neurobiology of learning and memory
• 影响因子: 2.7
• 作者: Ramirez,JulioJ;Campbell,David;Poulton,Winona;Barton,Cole;Swails,Jennifer;Geghman,Kindiya;Courchesne,StephanieL;Wentworth,Sean
• 通讯作者: Wentworth,Sean

Focal expression of mutated tau in entorhinal cortex neurons of rats impairs spatial working memory.

• DOI: 10.1016/j.bbr.2010.08.013
• 发表时间: 2011-01-01
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Ramirez, Julio J.;Poulton, Winona E.;Knelson, Erik;Barton, Cole;King, Michael A.;Klein, Ronald L.
• 通讯作者: Klein, Ronald L.

Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

• DOI: 10.1016/j.bbr.2012.04.034
• 发表时间: 2012-07-15
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: Mustroph, Martina L.;King, Michael A.;Klein, Ronald L.;Ramirez, Julio J.
• 通讯作者: Ramirez, Julio J.