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: 9380563
• 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 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9380563
• 关键词: Affect; Amblyopia; Animals; Arousal; Attention; Behavioral; Brain; Chemosensitization; Chronic; Development; Employee Strikes; 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 行为状态，例如睡眠和唤醒深刻影响 新皮层电路，但这些状态的功能在经验依赖性方面变化 发展和可塑性仍然存在争议。有影响力的理论，即突触稳态 假设（或害羞），睡眠的提案可用于体内稳态“重新归一化”突触 优势/发射速率受到醒来状态的经验依赖性变化的影响。 我的实验室研究了稳定视觉皮质内射击速率的体内平衡机制 微电路，可以在自由行为的动物的主要视觉皮层（V1）中跟踪此过程。 我们已经表明，通过单眼视觉剥夺（MD）在 单眼V1最初会抑制射击（1-2D MD），但是发射速率随后反弹以控制 在2 d期（MD3-4）任务中的水平继续进行。这种射击的恢复是 通过突触将兴奋性突触缩放到金字塔神经元上，部分完成 在V1中。我们可以遵循此过程，以使用慢性记录在 自由表现的动物在短暂的睡眠和唤醒之间骑自行车，使我们能够 直接确定在睡眠期间还是在 唤醒。出人意料的是，我们发现上升率稳态（向上FRH）发生 在每次主动唤醒中逐渐逐渐被抑制 （Hengen等，2016）。与害羞的假设形成鲜明对比的是，安排上的安装固定态 可塑性发生在唤醒期间，而不是睡觉。在这里，我们建议将这些发现扩展到 向下稳态可塑性，以探索唤醒/睡眠状态的特征 启用/抑制稳态可塑性，并确定是否相反的可塑性 （例如Hebbian LTP和突触降尺度）被隔离为不同的行为状态。 这些实验有望阐明皮质生理的基本特征，并阐明 阐明在协调突触可塑性中睡觉和醒来的大脑状态的功能 新皮层电路中的诱导。