Circuit Mechanisms of Cortical Synchronizations

描述（由申请人提供）： 拟议的研究旨在阐明导致UP状态产生的皮层内的细胞机制。UP状态是哺乳动物大脑中神经元集合的一种独特类型的同步激活，其中神经元组同步去极化数百毫秒，并在此期间激发动作电位。它们与感觉输入和运动输出等神经功能有关。同样重要的是，参与UP状态的神经元的集合似乎是稳定的，因为相同的局部细胞群在重复的场合以相同的顺序放电。这些神经系综的刻板时空动力学表明，它们可能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，还有很多东西需要了解。该应用程序测试的假设，即神经元的UP状态合奏的成员本身是触发和维持自己的同步去极化的关键。我们提出了一系列的刺激和消融研究来验证这一假设。考虑到这些神经系综可能代表皮质功能中至关重要的模块化元素，它们的破坏可能导致神经活动的紊乱，如在包括癫痫在内的许多神经系统疾病中所观察到的。

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.