Mechanisms of Long-Term Depression in the Striatum

描述（由申请人提供）： 突触强度的长期变化被认为代表了学习和记忆的细胞相关性。在海马中，长时程增强（LTP）和长时程抑制（LTD）已被广泛研究，并已阐明了许多不同的机制，其中一些共存于同一突触。在纹状体中，突触功能的变化被认为与习惯形成等行为相关，也与帕金森病、亨廷顿病和药物成瘾等病理相关。然而，机制，甚至在这些突触的可塑性的类型，还没有得到充分的描述。 本研究的目的是检查LTD在背侧纹状体和腹侧延伸，核的背侧纹状体。一些研究发现了各种不同的和相互矛盾的结果，在这些领域的有限责任公司。为了检查背侧纹状体和背侧核中突触处存在的LTD的类型，将测试各种诱导方案和实验范例。然后将使用电生理记录结合分子技术（如病毒介导的基因转移）来研究LTD诱导和表达的具体机制。这些研究将为理解纹状体突触强度的长期变化如何与成瘾和神经退行性疾病等健康问题相关提供一个框架。

DESCRIPTION (provided by applicant): Long-term changes in synaptic strength are thought to represent a cellular correlate of learning and memory. In the hippocampus, long-term potentiation (LTP) and long-term depression (LTD) have been studied extensively, and a number of different mechanisms have been elucidated, some of which coexist at the same synapses. In the striatum, changes in synaptic function are thought to correlate with behaviors such as habit formation, as well as with pathologies such as Parkinson's and Huntington's disease and drug addiction. However, the mechanisms, or even the types of plasticities present at these synapses, have not been fully described. The goal of this research proposal is to examine LTD in both the dorsal striatum and its ventral extension, the nucleus accumbens. A number of studies have found various and conflicting results regarding LTD in these areas. To examine the types of LTD present at synapses in both dorsal striatum and nucleus accumbens, various induction protocols and experimental paradigms will be tested. Specific mechanisms of LTD induction and expression will then be studied using electrophysioiogical recordings combined with molecular techniques such as viral-mediated gene transfer. These studies will provide a framework for understanding how long-term changes in synaptic strength in the striatum are related to such health issues as addiction and neurodegenerative disease.