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

基本信息

批准号：
10396620
负责人：
GINA G TURRIGIANO
金额：
$ 48.43万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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.

项目概要睡眠和觉醒等行为状态深刻影响活动模式和神经调节基调在新皮质回路内，但这些状态的功能会根据学习和经验而变化可塑性仍然存在争议，有人认为尾流是赫布机制发挥作用的时候，而睡眠有助于稳态“重新正常化”受到干扰的突触强度/放电率我们研究了清醒状态下的经验依赖性变化。稳定初级视觉皮层（V1）内的放电率和电路功能，并可以自由地跟踪这一过程行为啮齿类动物通过单眼视觉剥夺（MD）抑制放电（1- 2d MD），但尽管持续进行 MD，但放电率会在 2 d 时间内反弹至控制水平。使用 MD 和重开眼 (ER) 范式扰乱另一个方向的发射，并观察到 ER 增强了放电率，并再次缓慢恢复到基线值，这种“放电率稳态”就是这样的。通过将兴奋性突触放大或缩小到锥体神经元来完成部分在 V1 中，我们可以在自然睡眠和自然睡眠之间循环的自由行为动物中遵循这个过程。唤醒，以确定何时直接发生在最后一个资助期间的稳态恢复。做出了令人惊讶的发现，即向上和向下的放电率稳态受到相反的调节睡眠和唤醒状态：在每次主动唤醒期间逐渐发生向上并被睡眠抑制，而向下则由睡眠启用并由唤醒抑制。我们的工作表明睡眠和唤醒状态是不同的。对于控制稳态可塑性至关重要，并起到隔离向上和向下稳态的作用如何机械地实现这一过程是完全未知的。这种分离可能发挥的作用。在这里，我们建议确定清醒/睡眠状态的特征。启用/抑制放电率稳态，并测试潜在的突触可塑性是否机制本身是由睡眠和唤醒直接控制的。最后，深入了解。这种门控的行为/功能后果，我们建议测试睡眠和唤醒如何协调赫布这些实验有望在视觉依赖学习任务中实现 V1 内的稳态可塑性。阐明视觉皮层生理学的基本特征，并阐明睡眠和睡眠的功能学习过程中协调突触可塑性的唤醒状态。