Interneuron Diversity and Hippocampal Network Dynamics

描述（由申请人提供）：海马体是涉及 在更高的认知功能，如学习和记忆， 患有重要的神经系统疾病，如癫痫，精神分裂症， 老年痴呆症 海马的GABA能中间神经元显示出广泛的解剖学特征和 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、索马，以及 主要神经元的近端和远端树突。这种解剖学上的特异性 被认为与不同的功能角色有关。 大多数中间神经元已经在静态网络中进行了“体外”研究 条件，也就是说，从静态切片，缺乏类型的 可能发生在“体内”的电路活动。“因此， GABA能中间神经元与特异性突触后靶点的相互作用 结构域的生理或病理相关状态期间， 网络还不太了解。 因此，本研究的主要目标是重新评估功能性 中间神经元多样性和GABA能输入结构域特异性在 类似于大脑中“体内”发生的节律的活动。我们会研究 中间神经元多样性和结构域特异性GABA能输入在 海马同步爆发，这与更高的认知活动有关 在正常的大脑中，但在癫痫患者中可以发展到病理水平 条件 我们将把我们的项目集中在三个具体目标：（一）我们将测试 假设体周和树突GABA能输入调节不同 网络功能，（ii）我们将测试网络驱动的假设， 单个锥体细胞的爆发可以由特定的 最后，（iii）我们将测试突触的假设， 特定的中间神经元集合的特性控制GABA能神经元 在网络活动期间输入。 将不同的中间神经元和GABA能输入与清除功能联系起来， 对大脑皮层网络的组织原理有了重要的认识 在正常的大脑和疾病期间。

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.