GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior
GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior
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DOI：
10.1073/pnas.2010168118
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发表时间：
2021-02-09
影响因子：
11.1
通讯作者：
Mieda, Michihiro
中科院分区：
文献类型：
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作者：
Maejima, Takashi;Tsuno, Yusuke;Mieda, Michihiro
视交叉上核（SCN）是由多种γ -氨基丁酸（GABA）能神经元和神经胶质细胞组成的网络结构，是哺乳动物昼夜节律中枢起搏器。然而，gaba介导的信号在SCN网络中的作用仍然存在争议。在这里，我们报告了小鼠的昼夜节律明显受损，在精氨酸抗利尿素（AVP）产生的神经元中存在特异性缺失的水疱GABA转运体。这些小鼠表现出GABA(A)受体介导的SCN神经元突触传递的昼夜节律紊乱，并且由于早晚运动活动间隔的延长，昼夜行为节律的活动时间明显延长。SCN外植体的PER2::LUC成像和SCN AVP神经元细胞内Ca2+的体内记录显示，SCN神经元分子昼夜节律振荡的同步性没有显著改变，而SCN分子钟与昼夜运动活动的相位关系却发生了显著改变。相比之下，体内SCN神经元的日常神经元活动明显显示出与游离的早晚运动活动相关的双峰模式。因此，来自AVP神经元的gaba能传递调节了SCN神经元放电的时间，从而暂时将昼夜节律行为限制在SCN分子钟的适当时间窗口内。
The suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, is a network structure composed of multiple types of gamma-aminobutyric acid (GABA)-ergic neurons and glial cells. However, the roles of GABA-mediated signaling in the SCN network remain controversial. Here, we report noticeable impairment of the circadian rhythm in mice with a specific deletion of the vesicular GABA transporter in arginine vasopressin (AVP)-producing neurons. These mice showed disturbed diurnal rhythms of GABA(A) receptor-mediated synaptic transmission in SCN neurons and marked lengthening of the activity time in circadian behavioral rhythms due to the extended interval between morning and evening locomotor activities. Synchrony of molecular circadian oscillations among SCN neurons did not significantly change, whereas the phase relationships between SCN molecular clocks and circadian morning/evening locomotor activities were altered significantly, as revealed by PER2::LUC imaging of SCN explants and in vivo recording of intracellular Ca2+ in SCN AVP neurons. In contrast, daily neuronal activity in SCN neurons in vivo clearly showed a bimodal pattern that correlated with dissociated morning/evening locomotor activities. Therefore, GABAergic transmission from AVP neurons regulates the timing of SCN neuronal firing to temporally restrict circadian behavior to appropriate time windows in SCN molecular clocks.