Mechanisms for Sleep-Dependent Cortical Plasticity

描述(由申请人提供)：最近的研究揭示了睡眠在学习、记忆和皮质可塑性中的关键作用。我们先前已经证明，睡眠增强了眼优势可塑性(OOP)，这是一种由单眼剥夺(MD)在发育关键时期触发的体内突触重构形式。MD后睡眠期间初级视皮层的突触后活动对这一过程至关重要。然而，快速眼动(REM)和非快速眼动(NREM)睡眠对OOP的相对贡献尚不清楚，睡眠介导的ODP的确切细胞内机制也是未知的。ODP病的早期阶段与关键时期的视皮层长期抑制(LTD)和长期增强(LTP)有共同的关键特征。睡眠可能通过类似于LTD和/或LTP的机制来增强ODP值。本研究的目的是首先阐明REM和NREM睡眠在这一过程中的作用，其次研究LTP样可塑性机制和LTD样可塑性机制对睡眠依赖的ODP值的贡献。为了测试REM和NREM睡眠在ODP中的作用，我们将在一段时间的MD之后选择性地操纵这些睡眠阶段。为了确定睡眠是否通过LTD样或LTP样机制增强ODP值，我们将测试在MD睡眠后的视皮层中阻断蛋白磷酸酶或激酶通路的效果--分别对LTD或LTP至关重要。虽然睡眠的主要功能仍不清楚，但它在学习和记忆中的作用已经成为一个越来越令人感兴趣的领域。睡眠增强的机制很可能也是睡眠对其他类型的学习和记忆的影响的基础；了解睡眠在睡眠增强中的作用将进一步加深我们对其在认知功能中的作用的理解。我们的发现可能对服用影响睡眠结构的药物的患者以及那些受到失眠和其他日益普遍的睡眠障碍影响的患者具有重要意义。

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.