Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep
Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep
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DOI：
10.1038/nature19756
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发表时间：
2016-09-29
期刊：
影响因子：
64.8
通讯作者：
Bourque, C. W.
中科院分区：
文献类型：
--
作者：
Gizowski, C.;Zaelzer, C.;Bourque, C. W.
昼夜节律已经进化到能够预测并使动物适应地球24小时光周期的限制(1)。虽然在视交叉上核(SCN)的时钟神经元中建立周期性的分子过程已经被很好地理解，但从中央时钟发出的轴突投射驱动行为节律的机制尚不清楚(2-4)。在这里，我们表明，在小鼠的睡眠时间(Zeitgeber Time，ZT0-12)之前，水分摄入量的增加完全是由中枢时钟推动的，而不是由生理需求驱动的。否认这种激增的小鼠在睡眠期接近尾声时经历了严重的脱水，这表明这种水分摄入有助于维持夜间的水矿物质平衡。此外，这种效应特别依赖于SCN加压素(VP)神经元的活动，这些神经元投射到OVLT(终板血管有机体)中的干渴神经元，在那里VP作为神经递质被释放。SCN VP神经元在预期期(ZT21.5-23.5)开始电活动，并通过激活突触后VP V1a受体和下游的非选择性阳离子通道去极化和兴奋OVLT神经元。在预期期(基础期；ZT19.5-21.5)之前，光遗传诱导释放VP，兴奋OVLT神经元，并促使水摄入量激增。相反，在预期期抑制VP释放的光遗传抑制抑制了OVLT神经元的放电，并阻止了相应的水摄入量的增加。我们的发现揭示了预见性口渴的存在，并证明这种行为是由中枢时钟神经元释放VP介导的兴奋性肽能神经传递所驱动的。
Circadian rhythms have evolved to anticipate and adapt animals to the constraints of the earth's 24-hour light cycle(1). Although the molecular processes that establish periodicity in clock neurons of the suprachiasmatic nucleus (SCN) are well understood, the mechanisms by which axonal projections from the central clock drive behavioural rhythms are unknown(2-4). Here we show that the sleep period in mice (Zeitgeber time, ZT0-12) is preceded by an increase in water intake promoted entirely by the central clock, and not motivated by physiological need. Mice denied this surge experienced significant dehydration near the end of the sleep period, indicating that this water intake contributes to the maintenance of overnight hydromineral balance. Furthermore, this effect relies specifically on the activity of SCN vasopressin (VP) neurons that project to thirst neurons in the OVLT (organum vasculosum lamina terminalis), where VP is released as a neurotransmitter. SCN VP neurons become electrically active during the anticipatory period (ZT21.5-23.5), and depolarize and excite OVLT neurons through the activation of postsynaptic VP V1a receptors and downstream non-selective cation channels. Optogenetic induction of VP release before the anticipatory period (basal period; ZT19.5-21.5) excited OVLT neurons and prompted a surge in water intake. Conversely, optogenetic inhibition of VP release during the anticipatory period inhibited the firing of OVLT neurons and prevented the corresponding increase in water intake. Our findings reveal the existence of anticipatory thirst, and demonstrate this behaviour to be driven by excitatory peptidergic neurotransmission mediated by VP release from central clock neurons.