Spiral dynamics in the cortex during seizure and sensory evoked activity

描述(由申请人提供)：这项研究的长期目标是了解持续癫痫事件和感觉处理中皮质神经元活动的组织。在这个提案中，我们将研究一种特殊形式的群体神经元活动，即螺旋波。螺旋波是自然界中普遍存在的可激发系统的特征，在流型的形成和流动动力学的组织中起着重要作用。在生物医学领域，螺旋波动力学在心脏电生理学中得到了广泛的研究，并极大地促进了我们对心律失常发生机制的理解。然而，令人惊讶的是，只有少数研究人员研究了大脑中的螺旋动力学。继我们最近在大鼠新皮质脑片中发现螺旋波之后，在这项计划中，我们将在实验上证实在癫痫样事件期间以及在感觉诱发和自发活动期间，啮齿动物新皮质中存在螺旋波。活体皮质有广泛的远距离连接，这是脑片中没有的。因此，有必要从实验上研究完整皮质中螺旋波的启动和维持，因为强大的远程丘脑和皮质连接可能会扰乱这些螺旋波的发展。提出了三个具体目标来研究大鼠感觉皮质和运动皮质中波与波的相互作用。目标1致力于改进电压敏感染料成像方法，以识别螺旋中心的相位奇点。目的2是研究癫痫样活动中不同皮质区域螺旋活动的发生率。目标3是研究感觉诱发活动和睡眠样波的螺旋动力学。研究大脑皮层的螺旋动力学将直接有助于理解癫痫发作活动的启动和维持。螺旋被认为是心脏组织中心律失常活动的主要贡献者，消除心脏中的螺旋一直是预防心脏纤颤的一种治疗策略。这个项目与NINDS的任务高度相关，应该有助于理解大脑皮质癫痫活动的启动和持续，这一活动扰乱了大约1%的美国人口的生活。

DESCRIPTION (provided by applicant): The long-term goal of this study is to understand the organization of cortical neuronal activity in sustained seizure events and in sensory processing. In this proposal, we will study a special form of population neuronal activity, namely, spiral waves. Spiral waves are a ubiquitous feature of excitable systems in nature, where they play a role in pattern formation and the organization of flow dynamics. Within biomedical science, spiral wave dynamics have been studied extensively in cardiac electrophysiology, and have greatly advanced our understanding of arrhythmogenic mechanisms. Surprisingly, however, only a few researchers have studied spiral dynamics in the brain. Following our recent discovery of spiral waves in rat neocortical slices, in this proposal, we will experimentally verify the existence of spiral waves in rodent neocortex in vivo during seizure-like events and during sensory evoked and spontaneous activity. Cortex in vivo has extensive long-range connections which are not present in brain slices. It is therefore necessary to experimentally examine the initiation and sustaining of spiral waves in intact cortex, given that strong long-range thalamocortical and corticocortical connections may disrupt the development of these spiral waves. Three Specific Aims are proposed to study wave-to-wave interactions in rat sensory and motor cortices. Aim 1 is devoted to improve voltage-sensitive dye imaging methods in order to identify phase singularities at the spiral center. Aim 2 is to examine the incidence rate of spirals during seizure-like activity in various cortical areas. Aim 3 is to investigate spiral dynamics during sensory-evoked activity and sleep-like waves. Studying spiral dynamics in the cortex will directly contribute to understanding of the initiation and sustaining of seizure activity. Spirals are known as a major contributor to arrhythmic activity in cardiac tissue, and extinguishing spirals in the heart has been a therapeutic strategy for preventing cardiac fibrillation. This project is highly relevant to the mission of the NINDS, and should contribute to the understanding of initiation and sustaining of epileptic activity in the cortex, which disturbs the life of about 1% of the US population.