Klett Nathan, Gompf Heinrich S, Allen Charles N, Cravetchi Olga, Hablitz Lauren M, Gunesch Ali N, Irwin Robert P, Todd William D, Saper Clifford B, Fuller Patrick M
Oregon Institute for Occupational Health Sciences, USA.
Neuroscience Graduate Program, USA.
Eur J Neurosci. 2024 Dec;60(11):6652-6667. doi: 10.1111/ejn.16582. Epub 2024 Nov 18.
The suprachiasmatic nucleus is the circadian pacemaker of the mammalian brain. Suprachiasmatic nucleus neurons display synchronization of their firing frequency on a circadian timescale, which is required for the pacemaker function of the suprachiasmatic nucleus. However, the mechanisms by which suprachiasmatic nucleus neurons remain synchronized in vivo are poorly understood, although synaptic communication is considered indispensable. Suprachiasmatic nucleus neurons contain the neurotransmitter GABA and express GABA receptors. This has inspired the hypothesis that GABA signalling may play a central role in network synchronization, although this remains untested in vivo. Here, using local genetic deletion, we show that disruption of GABA synaptic transmission within the suprachiasmatic nucleus of adult mice results in the eventual deterioration of physiological and behavioural rhythmicity in vivo and concomitant cellular desynchrony in vitro. These findings suggest that intercellular GABA signalling is essential for behavioural rhythmicity and cellular synchrony of the suprachiasmatic nucleus neural network.
视交叉上核是哺乳动物大脑的昼夜节律起搏器。视交叉上核神经元在昼夜节律时间尺度上表现出其放电频率的同步性，这对视交叉上核的起搏器功能是必需的。然而，尽管突触通讯被认为是不可或缺的，但视交叉上核神经元在体内保持同步的机制仍知之甚少。视交叉上核神经元含有神经递质γ-氨基丁酸（GABA）并表达GABA受体。这激发了一种假说，即GABA信号可能在网络同步中起核心作用，尽管这在体内仍未得到验证。在这里，我们通过局部基因缺失表明，成年小鼠视交叉上核内GABA突触传递的破坏会导致体内生理和行为节律的最终恶化以及体外伴随的细胞去同步化。这些发现表明，细胞间GABA信号对视交叉上核神经网络的行为节律和细胞同步至关重要。
