找实验方法,上脑声常谈
责编︱王思珍
“逻辑神经科学”一作面对面系列讲座
(第九期)
昼夜节律篇 & 生物钟篇 & 感知科学篇
讲座题目:生物钟协调内在状态与外界感知的神经机制 (Molecular and Circuit Mechanisms Mediating Clock Regulation of Internal States and Sensory Perception)
主讲人:刘强博士后 美国约翰斯·霍普金斯大学
主持人:王强强(王思珍) 主编 逻辑神经科学
时 间:2024年11月6日(星期三)20:00-21:00(北京时间)
赞 助:上海欣软(脑声常谈)
学术支持:《CNS Neuroscience & Therapeutics》、《Ibrain》、《Neuroprotection》、《Brain-X》、《Advanced Science》。
技术支持:蔻享学术直播平台
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讲座摘要(Abstract)
I mainly focused on using mWAKE as a genetic entrée to investigate the molecular and circuit basis of rhythmic behavior. We first showed that mWAKE acts as a clock-dependent brake on arousal during the night. Rather than a simple model whereby the clock acts in a uniform manner to promote arousal during an animal’s active phase and enhance sleep during their quiescent phase, we found that the clock has a mixed approach to generating rhythmic arousal. Our data suggest that specific molecules and circuits under clock control actively oppose the dominant sleep/arousal rhythms, in order to shape the appropriate level of arousal. Following this work, I focused on studying the physiological and molecular mechanisms related to a local brain oscillator in the lateral amygdala (LA) and how it rhythmically coordinates different behaviors. In addition to cyclical clock gene expression, brain oscillators should also exhibit rhythms of electrical activity. However, no genetic marker exists that labels electrically rhythmic neural circuits. In this project, we first showed that mWAKE is enriched in a molecularly-defined subregion of the LA (anterior-dorsal LA/adLA). Although the core clock protein PER2 cycles throughout the LA, we show that only mWAKE-positive, but not mWAKE-negative, adLA neurons exhibit rhythmic intrinsic excitability. Surprisingly, impairing clock function or glutamate signaling in adLAmWAKE neurons eliminates PER2 cycling in a non-cell autonomous manner throughout the LA. At a molecular level, the mechanisms mediating rhythmic excitability outside of the SCN are poorly understood. We show that mWAKE levels rise at night in adLAmWAKEneurons and upregulate BK current to inhibit the excitability of these cells at night. Finally, we show that, rather than modulating an individual behavior, adLAmWAKEneurons utilize distinct projections to produce clock- and mWAKE-dependent rhythmic changes in two different behaviors: touch sensitivity and internal anxiety-like behavior. Our investigation of the first discrete extra-SCN brain oscillator also reveals new insights into the nature of the circadian timing network.
主讲人简介:
刘强
(照片提供自刘强本人)
刘强,本科及博士均毕业于上海大学,现为约翰斯·霍普金斯大学的博士后,主要研究领域为睡眠与生物钟。他的主要研究成果以第一作者发表在《Neuron》、《Nature Communications》、《Molecular Neurobiology》等期刊上。
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