Dynamic Properties of Elementary Inhibitory Circuits

描述(申请人提供)：前馈抑制电路是皮层神经元突触抑制的主要来源。然而，它们控制大脑皮层神经元活动的具体方式却鲜为人知。本研究的目的是探讨丘脑传入激活的前馈抑制回路控制皮层神经元兴奋性的机制。我们将检验这样的假设，即丘脑-皮质前馈抑制减少了皮质神经元的整合时间窗口，并加强了丘脑和皮质之间信号传输的时间保真度。 这项建议有两个目标：目标1解决丘脑-皮质前馈抑制在控制皮质神经元的整合时间窗口和棘波计时中的作用。目的2探讨丘脑皮质前馈抑制的细胞机制。这些实验将在急性小鼠丘脑皮质切片上使用电生理学和形态学技术进行。 这项研究将深入了解前馈抑制的功能作用，以及神经元网络平衡兴奋和突触抑制的机制。对控制皮层兴奋性的机制的深入了解可能有助于开发旨在防止皮层区域癫痫发生的治疗方法。

DESCRIPTION (provided by applicant): Feed-forward inhibitory circuits are a major source of synaptic inhibition to cortical neurons. The specific means by which they control the activity of cortical neurons is, however, poorly understood. The goal of this proposal is to address the mechanism by which feed-forward inhibitory circuits activated by thalamic afferents control the excitability of cortical neurons. We will test the hypothesis that thalamo-cortical feed-forward inhibition reduces the integration time window of cortical neurons, and enforces temporal fidelity of signal transmission between the thalamus and the cortex. This proposal has two aims: Aim 1 addresses the role of thalamo-cortical feed-forward inhibition in controlling the integration time window and spike timing of cortical neurons. Aim 2 addresses the cellular mechanism of thalamo-cortical feed-forward inhibition. The experiments will be performed on acute mouse thalamo-cortical slices using electrophysiological and morphological techniques. This study will provide insight into the functional role of feed-forward inhibition and the mechanisms by which neuronal networks balance excitation with synaptic inhibition. A deeper understanding of the mechanisms that control cortical excitability may contribute to the development of therapies aimed at preventing epileptogenesis in cortical areas.