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.

项目概要 睡眠和觉醒等行为状态深刻影响体内的活动模式 新皮质回路，但这些状态的功能变化依赖于经验 突触稳态是一个有影响力的理论，但仍存在争议。 假设（或 SHY），提出睡眠有助于稳态“重新正常化”突触 强度/发射率受到清醒状态下依赖于经验的变化的干扰。 我的实验室研究稳定视觉皮层内放电率的稳态机制 微电路，并且可以跟踪自由行为动物的初级视觉皮层（V1）中的这一过程。 我们已经证明，单眼视觉剥夺（MD）会扰动放电率 单眼 V1 最初抑制放电（MD 1-2d），但放电率随后反弹以控制 尽管持续 MD，但在 2 d 期间内的水平 (MD3-4) 仍处于恢复状态。 部分通过将兴奋性突触放大到锥体神经元上来完成 V1. 我们可以使用慢性记录来跟踪放电率稳态的过程。 行为自由的动物在短暂的睡眠和清醒之间循环，使我们能够 直接确定恢复的稳态是否发生在睡眠期间或期间 令人惊讶的是，我们发现发生了向上放电率稳态（向上FRH）。 在每次主动唤醒期间逐渐增强，但在安静唤醒和睡眠期间受到抑制 （Hengen 等人，2016）因此，与 SHY 假说形成鲜明对比的是，向上稳态。 可塑性发生在清醒期间，而不是睡眠期间。我们建议将这些发现扩展到睡眠期间。 向下的稳态可塑性，探索清醒/睡眠状态的特征 启用/抑制稳态可塑性，并确定是否存在相反形式的可塑性 （例如 Hebbian LTP 和突触缩减）被分为不同的行为状态。 这些实验有望阐明皮质生理学的基本特征，并 揭示睡眠和清醒大脑状态在协调突触可塑性中的功能 新皮质回路内的感应。