Spiral dynamics in the cortex during seizure and sensory evoked activity

描述（由申请人提供）：本研究的长期目标是了解持续癫痫发作事件和感觉处理中皮层神经元活动的组织。在这个提议中，我们将研究一种特殊形式的群体神经元活动，即螺旋波。螺旋波是自然界中可激系统的普遍特征，在模式形成和流动动力学组织中起着重要作用。在生物医学科学中，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。根据我们最近在大鼠新皮层切片中发现的螺旋波，在本提案中，我们将通过实验验证啮齿动物新皮层在体内癫痫样事件和感觉诱发和自发活动期间存在螺旋波。活体皮层具有广泛的远程连接，这在脑切片中是不存在的。因此，有必要通过实验研究完整皮层中螺旋波的开始和维持，因为强的长时间丘脑皮质和皮质皮质连接可能会破坏这些螺旋波的发展。提出了研究大鼠感觉和运动皮层波对波相互作用的三个具体目的。目的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是检查在不同皮质区域的癫痫样活动中螺旋的发生率。目的3是研究感觉诱发活动和睡眠样波期间的螺旋动力学。研究皮层中的螺旋动力学将直接有助于理解癫痫发作活动的开始和持续。众所周知，螺旋是心脏组织中心律失常活动的主要原因，而在心脏中扑灭螺旋一直是预防心脏颤动的治疗策略。该项目与NINDS的任务高度相关，并应有助于理解大脑皮层癫痫活动的开始和维持，这种活动扰乱了约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.