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: 10209082
• 负责人: GINA G TURRIGIANO
• 金额: $ 49.44万
• 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 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10209082
• 关键词: Affect; Amblyopia; Animals; Arousal; Attention; Behavior; Behavioral; Brain; Excitatory Synapse; Eye; Funding; Gryllidae; Homeostasis; Human; Image; Influentials; Learning; Light; Long-Evans Rats; Neocortex; Pattern; Physiology; Population; Process; Resolution; Rodent; Role; Sensory; Sleep; Source; Synapses; Synaptic plasticity; Testing; V1 neuron; Vision; Visual; Visual Cortex; Visual impairment; Work; area striata; basal forebrain; cholinergic; design; effective therapy; experience; experimental study; hippocampal pyramidal neuron; improved; in vivo; insight; learned behavior; monocular; neocortical; neuroregulation; non rapid eye movement; optogenetics; response; restoration; scale up; segregation; theories; visual deprivation

Project Summary Behavioral states such as sleep and wake profoundly affect the patterns of activity and neuromodulatory tone within neocortical circuits, but the function of these state changes on learning and experience-dependent plasticity remain controversial. It has been postulated that wake is when Hebbian mechanisms are engaged, while sleep serves to homeostatically “renormalize” synaptic strengths/firing rates that were perturbed by experience-dependent changes in the waking state. We study the homeostatic plasticity mechanisms that stabilize firing rates and circuit function within primary visual cortex (V1), and can track this process in freely behaving rodents. Perturbing firing through monocular visual deprivation (MD) initially suppresses firing (1- 2d MD), but firing rates then rebound to control levels over a 2 d period despite continued MD. Further, we can perturb firing in the other direction using an MD followed by eye re-opening (ER) paradigm, and observed that firing rates are potentiated by ER and again slowly return to baseline values. This ‘firing rate homeostasis’ is accomplished in part through synaptic scaling up or down of excitatory synapses onto pyramidal neurons within V1. We can follow this process in freely behaving animals cycling between natural bouts of sleep and wake, to directly determine when the homeostatic restoration of firing occurs. In the last funding period we made the surprising discovery that upward and downward firing rate homeostasis are oppositely regulated by sleep and wake states: upward occurs gradually during each bout of active wake and is suppressed by sleep, while downward is enabled by sleep and suppressed by wake. Our work reveals that sleep and wake states are critically important for gating homeostatic plasticity, and act to segregate upward and downward homeostatic processes into distinct behavioral states. How this is accomplished mechanistically is entirely unknown, as is the function this segregation might serve. Here we propose to determine the features of waking/sleeping states that enable/suppress firing rate homeostasis, and to test whether the underlying synaptic plasticity mechanisms are themselves directly gated by sleep and wake. Finally, to gain insight into the behavioral/functional consequences of this gating, we propose to test how sleep and wake orchestrate Hebbian and homeostatic plasticity within V1 during a vision-dependent learning task. These experiments promise to illuminate fundamental features of visual cortical physiology, and to shed light on the function of sleep and wake states in coordinating synaptic plasticity during learning.

项目摘要 睡眠和唤醒等行为状态会深刻影响活动和神经调节语调的模式 在新皮质电路中，但是这些状态的功能在学习和经验依赖性方面变化 塑性仍然存在争议。据推测，唤醒是赫比安机制订婚的时候， 虽然睡眠可用于体内稳态“重新归一化”突触强度/发射率 醒来状态的经验依赖性变化。我们研究了稳态可塑性机制 稳定初级视觉皮层（V1）内的点火率和电路功能，并可以自由地跟踪此过程 行为啮齿动物。通过单眼视觉剥夺（MD）扰动发射最初抑制发射（1- 2D MD），但是发射速率随后反弹到控制水平的2D时期目的地继续MD。此外，我们可以 使用MD朝另一个方向发射，然后重新开放（ER）范式，并观察到 ER的发射速率可能会产生，并再次慢慢返回基线值。这种“发射率稳态”是 通过突触将兴奋性突触上或向下缩放到金字塔神经元中，部分完成 在V1中。我们可以在自由行为的动物中遵循这一过程，在自然的睡眠和 唤醒，直接确定何时发生射击的稳态恢复。在最后的资金期内 令人惊讶的发现，向上和向下的点火率体内平衡受到相反的监管 睡眠和唤醒状态：在每次主动唤醒期间逐渐向上发生，并被睡眠抑制， 虽然通过睡眠来启用向下并被唤醒抑制。我们的工作表明睡眠和唤醒状态是 至关重要的是对稳态可塑性至关重要，并采取行动以向上和向下隔离稳态 将过程分为不同的行为状态。机理如何完成这是完全未知的， 该隔离可能起到的功能。在这里，我们建议确定醒来/睡眠状态的特征 这样可以启用/抑制点火率稳态，并测试是否基础突触可塑性 机制本身是直接通过睡眠和唤醒门控。最后，了解 该门控的行为/功能后果，我们建议测试睡眠和唤醒Hebbian的方式 在依赖视觉的学习任务中，V1内的稳态可塑性。这些实验有望 照亮视觉皮质生理学的基本特征，并阐明睡眠和睡眠功能 在学习过程中，唤醒状态在协调的突触可塑性中。