褪黑素对NREM睡眠期内嗅皮层浅层慢波振荡的调控及机制研究

The neural activity in the superficial layers of entorhinal cortex exhibits a prominent circadian variation, which is closely related to the learning and memory,. The superficial layers of entorhinal cortex display high excitability during wakefulness, which facilitates the memory encoding. While the superficial layers of entorhinal cortex exhibit low excitability and slow oscillations during NREM sleep, which contributes to synaptic homeostasis. So far, the mechanisms underlying the slow oscillations in the superficial layers of entorhinal cortex during NREM sleep is still unclear. Previous studies found that the level of melatonin, secreted by pineal gland under the control of the circadian pacing-making center- suprachiasmatic nucleus, is very high during sleep. Our previous studies demonstrated that superficial layers of entorhinal cortex express melatonin receptors, and melatonin can dramatically inhibit the activity of excitatory neurons in superficial layers of entorhinal cortex. On these basis, in this project we will comprehensively use morphological, electrophysiological, molecular genetic approaches and behavioral tests and firstly investigate the role for melatonin in regulation of slow wave oscillations in superficial layers of entorhinal cortex. Then we will clarify the mechanisms underlying how the melatonin regulation of slow oscillations at the cellular level and micro-circuitry level, which is associated the synchronization of neural network ensemble. Lastly, we will explore how the melatonin affect the slow oscillations-related synaptic homeostasis and episodic learning and memory. The aim of this project is to clarify the neural mechanisms underlying the slow oscillations, which might further reveal the biological basis of learning and memory from the perspective of biological rhythms.

内嗅皮层浅层的活动呈现典型的节律性，与学习记忆密切相关。觉醒时其兴奋性较高，有利于记忆编码。NREM睡眠时其神经元兴奋性下调，呈现慢波振荡，促进突触稳态恢复。迄今，NREM睡眠期内嗅皮层浅层慢波振荡发生的机制尚不清楚。回顾文献，NREM睡眠期机体通过生物钟起搏点-视交叉上核对松果体分泌的褪黑素进行调控，使其分泌在睡眠期高。本室前期实验证实，内嗅皮层浅层有褪黑素受体表达，褪黑素可抑制其主要兴奋性神经元活动。在此基础上，本项目拟综合应用形态学、电生理学、分子遗传学及行为学检测等技术，阐明褪黑素对内嗅皮层浅层慢波振荡的调控作用；在单细胞及细胞集群同步化所依赖的功能微环路水平上，分析褪黑素调控慢波振荡的机制；最后，我们将研究褪黑素如何调控慢波振荡相关的突触稳态和情景学习记忆。本项目旨在阐明内嗅皮层浅层慢波振荡的发生机制，以期从睡眠觉醒生物节律角度进一步揭示学习记忆的生物学基础。