Circuit Mechanisms of Cortical Synchronizations

描述(由申请人提供)： 这项拟议的研究旨在阐明导致UP状态产生的皮质内的细胞机制。UP状态是哺乳动物大脑中神经元整体的一种独特的同步激活类型，在此过程中，一组神经元被同步去极化数百毫秒，并在此期间激发动作电位。它们与神经功能有关，如感觉输入和运动输出。同样重要的是，参与UP状态的神经元集合似乎是稳定的，因为相同的局部细胞组在重复的情况下以相同的序列激发。这些神经集合的刻板的时空动力学表明，它们可能起源于对其组织和功能至关重要的潜在神经元连接模式。然而，关于这些UP状态是如何触发或维持的，仍有很多需要了解。这一应用测试了一种假设，即作为UP状态集合成员的神经元本身对于触发和维持自身的同步去极化至关重要。我们提出了一系列刺激和消融研究来验证这一假说。鉴于这些神经集合可能代表在皮质功能中至关重要的模块元件，它们的破坏可能会导致神经活动的混乱，就像在包括癫痫在内的许多神经疾病中观察到的那样。

DESCRIPTION (provided by applicant): The proposed studies are aimed at elucidating the cellular mechanisms within cortex that lead to the generation of UP states. UP states are a distinct type of synchronous activation of neuronal ensembles in mammalian brain in which groups of neurons are synchronously depolarized for hundreds of milliseconds and fire action potentials during that time. They have been associated with neural function such a sensory input and motor output. As importantly, the ensemble of neurons participating in an UP state appears to be stable, in that the same local group of cells fires in the same sequence on repeated occasions. The stereotyped spatiotemporal dynamics of these neural ensembles suggest that they may arise from underlying neuronal connectivity patterns that are critical for their organization and function. However, much remains to be learned about how these UP states are triggered or maintained. This application tests the hypothesis that neurons that are members of UP state ensembles are themselves critical for triggering and maintaining their own synchronous depolarization. We propose a series of stimulation and ablation studies to test this hypothesis. Given the possibility that these neural ensembles likely represent modular elements critical in cortical function, their disruption may lead to disorganization of neural activity as is observed in a number of neurological disorders including epilepsy.