Exploratory studies of spontaneous cortical activity in visual cortical development

总结 我们的总体目标是研究视觉皮层（V1）的发育过程， 但相反，它们受到内源性神经元活动的影响。这种最初的经验独立 发育阶段对于形成随后被 由视觉经验塑造而成。新生哺乳动物的大部分时间都在快速眼动（REM）中度过。 睡眠，这表明这种大脑状态提供了一个内源性活动的主要来源，以发展 个脑袋这个想法还没有被深入探讨使用目前的神经生物学方法。拟议 因此，探索性研究将为睡眠和经验如何共同塑造 以及婴儿期不正常的睡眠如何对大脑发育产生不利影响。到 为了实现我们的目标，我们将测量V1活动在发展雪貂，以确定是否自发活动在快速眼动 睡眠是以一种可以指导或维持发育中的回路的方式来构造的。然后我们将直接测试 REM睡眠V1活动在视觉反应特性发展中的作用。这将是完成 使用多导睡眠描记术、遗传编码钙指示剂成像和光遗传学的组合 （适合小型哺乳动物）。本A1提案已根据 事先审查。

Summary Our overall goal is to investigate developmental processes in visual cortex (V1) that do not require visual experience but are instead influenced by endogenous neuronal activity. This initial experience-independent stage of development is critically important for the formation of rudimentary circuits that are subsequently sculpted by visual experience. Neonatal mammals spend most of their time in rapid-eye-movement (REM) sleep, which suggests that this brain state provides a principal source of endogenous activity to the developing brain. This idea has not been explored in depth using current neurobiological methods. The proposed exploratory research will thus provide important new insights into how sleep and experience together shape developing circuitry and how abnormal sleep during infancy may adversely impact brain development. To achieve our goal, we will measure V1 activity in developing ferrets to determine if spontaneous activity in REM sleep is structured in a manner that may instruct or maintain developing circuits. We will then directly test the role of REM sleep V1 activity in the development of visual response properties. This will be accomplished using a combination of polysomnography, genetically encoded calcium indicator imaging and optogenetics (optimized for small mammals). This A1 proposal has been revised in accordance with recommendations from prior review.