Astrocytes Control Circadian Timekeeping in the Suprachiasmatic Nucleus via Glutamatergic Signaling.
Astrocytes Control Circadian Timekeeping in the Suprachiasmatic Nucleus via Glutamatergic Signaling.
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DOI：
10.1016/j.neuron.2017.02.030
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发表时间：
2017-03-22
期刊：
影响因子：
16.2
通讯作者：
Hastings MH
中科院分区：
文献类型：
--
作者：
Brancaccio M;Patton AP;Chesham JE;Maywood ES;Hastings MH
下丘脑的视交叉上核(SCN)协调哺乳动物的日常生理和行为节律。其基因表达和电活动的昼夜节律(∼24小时)振荡是内在产生的，并可以在时间隔离中无限持续。这种健壮和有弹性的计时通常被认为是其神经元内在连接的产物。在这里，我们表明神经元只构成SCN时钟的一半，即昼夜代谢活跃的时钟。相比之下，SCN星形胶质细胞在昼夜节律时活跃，此时它们通过调节细胞外谷氨酸水平来抑制SCN神经元的活动。这种谷氨酸能神经胶质传递是由背侧SCN的神经元通过含有NR2C亚单位的特定突触前NMDA受体组件感受到的。值得注意的是，SCN星形胶质细胞内时钟的体细胞遗传重新编程能够重塑成年小鼠的昼夜行为节律。因此，SCN电路水平的计时起源于相互依赖和相互支持的星形胶质细胞-神经元信号。SCN神经元在昼夜活动，而星形胶质细胞在夜间活跃，星形胶质细胞直接细胞外谷氨酸的昼夜周期抑制SCN神经元-星形胶质细胞衍生的抑制是通过NMDAR2C复合体对SCN背侧SCN神经元的时钟遗传重新编程，星形胶质细胞重塑昼夜行为的视交叉上核(SCN)神经元负责哺乳动物的昼夜起搏。在这里，Brancaccio等人。证明SCN星形胶质细胞也具有起搏特性，并揭示它们如何通过与神经元伙伴的相互计时来设定昼夜节律。
The suprachiasmatic nucleus (SCN) of the hypothalamus orchestrates daily rhythms of physiology and behavior in mammals. Its circadian (∼24 hr) oscillations of gene expression and electrical activity are generated intrinsically and can persist indefinitely in temporal isolation. This robust and resilient timekeeping is generally regarded as a product of the intrinsic connectivity of its neurons. Here we show that neurons constitute only one “half” of the SCN clock, the one metabolically active during circadian daytime. In contrast, SCN astrocytes are active during circadian nighttime, when they suppress the activity of SCN neurons by regulating extracellular glutamate levels. This glutamatergic gliotransmission is sensed by neurons of the dorsal SCN via specific pre-synaptic NMDA receptor assemblies containing NR2C subunits. Remarkably, somatic genetic re-programming of intracellular clocks in SCN astrocytes was capable of remodeling circadian behavioral rhythms in adult mice. Thus, SCN circuit-level timekeeping arises from interdependent and mutually supportive astrocytic-neuronal signaling. SCN neurons are active during circadian day, but SCN astrocytes are active at night Astrocytes direct circadian cycles of extracellular glutamate to inhibit SCN neurons Astrocyte-derived inhibition is mediated by NMDAR2C complexes on dorsal SCN neurons Genetic re-programming of the clock in SCN astrocytes reshapes circadian behavior Neurons of the suprachiasmatic nucleus (SCN) are responsible for circadian pacemaking in mammals. Here, Brancaccio et al. demonstrate that SCN astrocytes also possess pacemaking properties and unravel how they set circadian tempo by reciprocal timing with their neuronal partners.