PDF(Pubmed)
Abstract：
The suprachiasmatic nucleus (SCN) is composed of functionally distinct subpopulations of GABAergic neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons, and which aspects result from neuronal interaction within a network. Here, we utilize in vivo miniaturized microscopy to measure fluorescent GCaMP-reported calcium dynamics in arginine vasopressin (AVP)-expressing neurons in the intact SCN of awake, behaving mice. We report that SCN AVP neurons exhibit periodic, slow calcium waves which we demonstrate, using in vivo electrical recordings, likely reflect burst firing. Further, we observe substantial heterogeneity of function in that AVP neurons exhibit unstable rhythms, and relatively weak rhythmicity at the population level. Network analysis reveals that correlated cellular behavior, or coherence, among neuron pairs also exhibited stochastic rhythms with about 33% of pairs rhythmic at any time. Unlike single-cell variables, coherence exhibited a strong rhythm at the population level with time of maximal coherence among AVP neuronal pairs at CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity for the SCN as a whole. These results demonstrate robust circadian variation in the coordination between stochastically rhythmic neurons and that interactions between AVP neurons in the SCN may be more influential than single-cell activity in the regulation of circadian rhythms. Furthermore, they demonstrate that cells in this circuit, like those in many other circuits, exhibit profound heterogenicity of function over time and space.
摘要：
视交叉上核（SCN）由功能上不同的GABA能神经元亚群组成，形成负责同步哺乳动物大多数生理和行为昼夜节律的神经网络。迄今为止,关于SCN节律性的哪些方面是由单个SCN神经元产生的，知之甚少，以及网络内的神经元相互作用会产生哪些方面。这里,我们利用体内微型化显微镜来测量清醒的完整SCN中精氨酸加压素（AVP）表达神经元的荧光GCaMP报道的钙动力学，表现老鼠。我们报道SCNAVP神经元表现出周期性，我们展示的缓慢的钙波，使用体内电记录，可能反映了爆炸射击。Further,我们观察到功能的实质性异质性，因为AVP神经元表现出不稳定的节律，人口水平的节律性相对较弱。网络分析揭示了相关的细胞行为，或连贯性，在神经元对中也表现出随机节律，约有33％的对在任何时候都有节律。与单细胞变量不同，在CT/ZT6和9时，AVP神经元对之间的最大一致性时间在群体水平上表现出强烈的节律，这与整个SCN的最大神经元活动时间一致。这些结果表明，随机节律神经元之间的协调存在强大的昼夜节律变化，并且SCN中AVP神经元之间的相互作用在昼夜节律的调节中可能比单细胞活性更具影响力。此外，他们证明了这个电路中的细胞，像许多其他电路一样，在时间和空间上表现出深刻的功能异质性。
