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。我们以前已经表明，睡眠增强眼优势可塑性（OOP），在发展的关键时期单眼剥夺（MD）触发的体内突触重塑的一种形式。在MD后睡眠期间，初级视觉皮层中的突触后活动对于这一过程至关重要。然而，快速眼动（REM）和非REM（NREM）睡眠对OOP的相对贡献是未知的，睡眠介导的ODP背后的精确细胞内机制也是未知的。ODP的早期阶段与关键期内视觉皮层的长时程抑制（LTD）和长时程增强（LTP）有着共同的特征。睡眠可能通过类似于LTD、LTP或两者的机制增强ODP。这些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样和LTD样可塑性机制对睡眠依赖性ODP的贡献。为了测试REM和NREM睡眠在ODP中的作用，我们将在MD一段时间后选择性地操纵这些睡眠阶段。为了确定睡眠是否通过LTD或LTP样机制增强ODP，我们将测试在MD后睡眠期间阻断蛋白磷酸酶或激酶通路（分别对LTD或LTP至关重要）对视觉皮层的影响。虽然睡眠的主要功能仍然是未知的，但它在学习和记忆中的作用已经成为一个越来越受关注的领域。ODP的睡眠增强机制可能也是睡眠对其他类型学习和记忆的影响的基础;了解睡眠在ODP中的作用将进一步了解其在认知功能中的作用。我们的研究结果可能对服用影响睡眠结构的药物的患者以及受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.