Department of Physiology, Institute of Brain and Intelligence, Third Military Medical University, Chongqing, 400038, China.
School of Basic Medical Sciences and IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
Adv Sci (Weinh). 2024 Oct;11(38):e2400253. doi: 10.1002/advs.202400253. Epub 2024 Aug 9.
High-frequency oscillatory activity in cognition-related neural circuits during wakefulness consistently induces the growth of dendritic spines and axonal terminals. Although these structural changes are essential for cognitive functions, it is hypothesized that if these newly expanded structures fail to establish functional connections, they may become superfluous. Sleep is believed to facilitate the reduction of such redundant structures to maintain neural homeostasis. However, the mechanisms underlying this pruning process during sleep remain poorly understood. In this study, that melatonin type 3 receptors (MTRs) are selectively expressed in the stellate neurons of the medial entorhinal cortex (MEC) is demonstrated, an area where high melatonin levels are detected during sleep. Activation of MTRs during sleep initiates the shrinkage of dendritic spines in stellate neurons by downregulating neural network activity and dephosphorylating synaptic proteins in the MEC. This process is disrupted when MTR expression is knocked down or when MTRs are blocked during sleep. Notably, interference with MTRs in the MEC during sleep impairs the acquisition of spatial memory but does not affect object memory acquisition following sleep. These findings reveal novel molecular mechanisms involving melatonin and MTRs in the regulation of dendritic spine shrinkage during sleep, which is crucial for the acquisition and consolidation of spatial memory.
在清醒状态下，与认知相关的神经回路中的高频振荡活动一致地诱导树突棘和轴突末梢的生长。尽管这些结构变化对于认知功能至关重要，但据推测，如果这些新扩展的结构未能建立功能连接，它们可能变得多余。人们认为睡眠有助于减少这些冗余结构以维持神经内稳态。然而，睡眠期间这种修剪过程的机制仍知之甚少。在这项研究中，证明了褪黑素 3 型受体 (MTRs) 选择性地表达在中隔核内的星状神经元中，在睡眠期间检测到高褪黑素水平的区域。在睡眠期间激活 MTRs 通过下调神经网络活动和去磷酸化 MEC 中的突触蛋白，启动星状神经元树突棘的收缩。当 MTR 表达被敲低或在睡眠期间阻断 MTR 时，该过程被打乱。值得注意的是，在睡眠期间干扰 MEC 中的 MTRs 会损害空间记忆的获得，但不会影响睡眠后物体记忆的获得。这些发现揭示了涉及褪黑素和 MTRs 在睡眠期间调节树突棘收缩的新的分子机制，这对于空间记忆的获得和巩固至关重要。
