“Brain state modulation of synaptic plasticity: role for sleep in homeostasis and the segregation of plasticity”
Despite the many advances in brain science, some very basic questions still remain. The role of sleep, for example, remains a puzzle. Mr. Cary’s research explores one long-held theory for the purpose of sleep, as a time for the brain to restore balance after the activity of the day.
Sleep is a widely expressed and conserved behavior across the animal kingdom. Despite its ubiquity and long history of scientific study, sleep – and more broadly the function of brain states – remains deeply mysterious. It is widely believed that a central purpose of sleep is its modulation of synaptic plasticity, however there is little agreement on the nature of this regulation. Specifically, there is disagreement on whether sleep primarily enables correlation-based plasticity mechanisms such as long-term potentiation (LTP), or homeostatic plasticity which serves the function of regulating overall synaptic strength to stabilize neuron and circuit function. One influential hypothesis, the synaptic homeostasis hypothesis (SHY), has motivated a lot of work concerning this question. SHY proposes that memories are formed during wake when animals actively sample their environment, primarily through Hebbian LTP-like mechanisms that cause a net potentiation of synapses. This process would saturate synapses if left unopposed, and subsequent sleep is proposed to be an offline state that allows neurons to scale down synaptic strengths through homeostatic plasticity. In these experiments I have used real-time sleep/wake detection, combined with in vivo optogenetic manipulation and ex vivo slice electrophysiology to provide insight on how sleep states regulate synaptic strength and plasticity. The following experiments are a direct test of the possibility that synaptic weights oscillate across basal sleep/wake cycles, which carefully control for cell type and circadian rhythm. Interestingly, patch recording data thus far show no difference in synaptic weights after periods of wake or sleep, while in vivo data suggests a modulation of excitability by sleep but no SHY-like oscillation. If synaptic weights do not oscillate across basal sleep cycles, it is still a compelling possibility that the induction of Hebbian and/or homeostatic plasticity is modulated by sleep or wake during experience-dependent plasticity, a possibility I will be directly testing in future in vivo experiments.