Mechanisms for Sleep-Dependent Cortical Plasticity

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION (provided by applicant): Recent studies have revealed a critical role for sleep in learning, memory, and cortical plasticity. We have previously shown that sleep enhances ocular dominance plasticity (OOP), a form of in vivo synaptic remodeling triggered by monocular deprivation (MD) during a critical period of development. Postsynaptic activity in the primary visual cortex during post-MD sleep is critical for this process. However, the relative contributions of rapid eye movement (REM) and non-REM (NREM) sleep to OOP are unknown, as are the precise intracellular mechanisms underlying sleep-mediated ODP. The early stages of ODP share key features with long-term depression (LTD) and long-term potentiation (LTP) in the visual cortex during the critical period. It is possible that sleep enhances ODP through mechanisms similar to LTD, LTP, or both. The goals of the proposed studies are first, to clarify the roles of REM and NREM sleep in this process, and second, to investigate the contribution of LTP-like and LTD-like plasticity mechanisms to sleep-dependent ODP. To test the roles of REM and NREM sleep in ODP, we will selectively manipulate these sleep stages following a period of MD. To determine whether sleep enhances ODP via LTD-like or LTP-like mechanisms, we will test the effects of blocking protein phosphatase or kinase pathways - critical for LTD or LTP, respectively - in the visual cortex during post-MD sleep. While the primary function of sleep is still unknown, its role in learning and memory has become an area of increasing interest. It is likely that the mechanisms underlying sleep enhancement of ODP also underlie sleep effects on other types of learning and memory;understanding the role of sleep in ODP will further our understanding of its role in cognitive function. Our findings may have important implications for patients taking medications that affect sleep architecture, and those affected by insomnia and other increasingly prevalent sleep disorders.