Gating of Firing Rate Homeostasis by Sleep and Wake States During Experience-Dependent Plasticity

经验依赖性可塑性期间睡眠和清醒状态对放电率稳态的门控

• 批准号: 9767198
• 负责人: GINA G TURRIGIANO
• 金额: $ 40.63万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9767198
• 关键词: Affect; Amblyopia; Animals; Arousal; Attention; Behavioral; Brain; Chemosensitization; Chronic; Development; Excitatory Synapse; Eye; Homeostasis; Human; Influentials; Light; Mental Depression; Neocortex; Pattern; Phase; Physiology; Population; Process; Sensory; Sleep; Source; Synapses; Synaptic plasticity; Testing; Vision; Visual; Visual Cortex; Visual impairment; area striata; basal forebrain; base; behavioral plasticity; cholinergic; design; effective therapy; experience; experimental study; hippocampal pyramidal neuron; in vivo; in vivo imaging; monocular; neocortical; restoration; scale up; theories; visual deprivation

PROJECT SUMMARY Behavioral states such as sleep and wake profound affect the patterns of activity within neocortical circuits, but the function of these state changes on experience-dependent development and plasticity remain controversial. An influential theory, the synaptic homeostasis hypothesis (or SHY), proposes that sleep serves to homeostatically “renormalize” synaptic strengths/firing rates that were perturbed by experience-dependent changes in the waking state. My lab studies the homeostatic mechanisms that stabilize firing rates within visual cortical microcircuits, and can track this process in primary visual cortex (V1) of freely behaving animals. We have shown that perturbing firing rates through monocular visual deprivation (MD) in monocular V1 initially suppresses firing (1-2d MD), but that firing rates then rebound to control levels over a 2 d period (MD3-4) despite continued MD. This restoration of firing is accomplished in part through synaptic scaling up of excitatory synapses onto pyramidal neurons within V1. We can follow this process of firing rate homeostasis using chronic recordings in freely behaving animals that are cycling between short bouts of sleep and wake, allowing us to directly determine whether the homeostatic restoration of firing occurs during sleep or during wake. Surprisingly, we found that upward firing rate homeostasis (upward FRH) occurs gradually during each bout of active wake, but is suppressed during quite wake and sleep (Hengen et al., 2016). Thus, in striking contrast to the SHY hypothesis, upward homeostatic plasticity happens during wake, not sleep. Here we propose to extend these findings to downward homeostatic plasticity, to explore the features of waking/sleeping states that enable/suppress homeostatic plasticity, and to determine whether opposing forms of plasticity (such as Hebbian LTP and synaptic downscaling) are segregated into distinct behavioral states. These experiments promise to illuminate a fundamental feature of cortical physiology, and to shed light on the function of sleeping and waking brain states in coordinating synaptic plasticity induction within neocortical circuits.

项目摘要 诸如睡眠和清醒等行为状态深刻地影响着内在的活动模式 新皮层回路，但这些状态的功能变化依赖于经验 发育和可塑性仍然存在争议。一个很有影响力的理论， 假说（或SHY）提出，睡眠有助于稳态“重新正常化”突触 强度/放电率被唤醒状态中的经验依赖性变化所干扰。 我的实验室研究的是稳定视觉皮层放电频率的自我平衡机制 微电路，并可以跟踪这一过程中的初级视觉皮层（V1）的自由行为的动物。 我们已经表明，通过单眼视觉剥夺（MD）的干扰放电率， 单眼V1最初抑制放电（1 - 2d MD），但放电率随后反弹至控制 水平超过2天的时间（MD3 - 4），尽管继续MD。这次恢复射击是 这部分是通过兴奋性突触在锥体神经元上的突触放大来实现的 在V1。我们可以通过长期记录来跟踪放电率稳态的过程， 自由行为的动物在短暂的睡眠和清醒之间循环，使我们能够 直接确定放电的稳态恢复是发生在睡眠期间还是发生在 醒来。令人惊讶的是，我们发现，向上放电率稳态（向上FRH）发生 在每一轮活跃的觉醒过程中逐渐地，但在安静的觉醒和睡眠过程中被抑制 （Hengen等人，2016年）。因此，与SHY假说形成鲜明对比的是， 可塑性发生在清醒时，而不是睡眠时。在这里，我们建议将这些发现扩展到 向下稳态可塑性，探索清醒/睡眠状态的特征， 启用/抑制稳态可塑性，并确定是否相反形式的可塑性 (such如Hebbian LTP和突触降尺度）被分离成不同的行为状态。 这些实验有望阐明皮层生理学的一个基本特征， 揭示了睡眠和清醒的大脑状态在协调突触可塑性中的作用 神经皮层回路内的感应。