Interneuron Diversity and Hippocampal Network Dynamics

描述(申请人提供)：海马体是受累的大脑区域 在较高的认知功能，如学习和记忆，通常是 受到重要神经疾病的影响，如癫痫、精神分裂症和 阿尔茨海默氏症。 海马的GABA能中间神经元表现出广泛的解剖学和 功能多样性。不同类型的中间神经元支配特定的 突触后结构域，如轴突起始段、胞体以及 主神经元近端和远端的树突。这种解剖学的特殊性 已经被认为与不同的功能角色有关。 大多数中间神经元都是在静态网络中“体外”研究的。 条件，也就是说，从缺乏类型的静止切片 很可能发生在“体内”的回路活动。因此， GABA能中间神经元与特定突触后靶点的相互作用 在生理或病理相关状态下的结构域 网络还没有被很好地理解。 因此，本研究的主要目的是重新评估功能 神经元间质多样性和GABA能输入域特异性在脑缺血-再灌注损伤中的作用 类似于大脑中“活体”发生的节奏的活动。我们会研究 神经元间多样性和区域特异性GABA能输入在脑发育过程中的作用 海马区同步爆发，与较高的认知活动有关 在正常大脑中，但在癫痫患者中可以进展到病理水平 条件。 我们的项目将集中于三个具体目标：(I)我们将测试 周围型和树突型GABA能传入调节不同的假说 网络功能，(Ii)我们将检验网络驱动的假设 单个锥体细胞的爆裂可以由特定的几组 中间神经元，最后，(Iii)我们将检验突触 特定中间神经元组的特性控制GABA能神经元的时间 网络活动期间的输入。 将不同的中间神经元和GABA能输入与清除功能联系起来可能 导致对大脑皮层网络组织原理的重要洞察 在正常大脑和疾病期间。

DESCRIPTION (provided by applicant): The hippocampus is a brain region involved in higher cognitive functions, such as learning and memory, and is often affected by important neurological illnesses like epilepsy, schizophrenia and Alzheimer's disease. GABAergic interneurons of the hippocampus display a wide anatomical and functional diversity. Distinct types of interneurons innervate specific postsynaptic domains such as the axon initial segment, soma, as well as the proximal and distal dendrites of principal neurons. This anatomical specificity has been suggested to relate to different functional roles. Most interneurons have been studied "in vitro" during static network conditions, that is to say, from quiescent slices that lack the type of circuitry activity that is likely to occur "in vivo." As a consequence, the interactions between GABAergic interneurons and specific postsynaptic target domains during physiologically- or pathologically-relevant states of the network are not well understood. Therefore, the primary goal of this research is to re-evaluate the functional roles of interneuron diversity and GABAergic input domain specificity during activity similar to rhythms occurring "in vivo" in the brain. We will study the role of interneuron diversity and domain specific GABAergic input during hippocampal synchronous bursting, which is related to higher cognitive activity in the normal brain, but can progress to pathological levels in epileptic conditions. We will focus our project on three specific aims: (i) we will test the hypothesis that perisomatic and dendritic GABAergic inputs regulate different network functions, (ii) we will test the hypothesis that network-driven bursting in individual pyramidal cells can be controlled by specific sets of interneurons, and, finally, (iii) we will test the hypothesis that synaptic properties of specific sets of interneurons control the timing of GABAergic input during network activity. Relating different interneurons and GABAergic inputs to clear functions may lead to important insight into the organizing principles of cortical networks in the normal brain and during disease.