Daily electrical activity in the master circadian clock of a diurnal mammal
Daily electrical activity in the master circadian clock of a diurnal mammal
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DOI：
10.1101/2020.12.23.424225
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发表时间：
2020-12
期刊：
影响因子：
7.7
通讯作者：
Beatriz Baño-Otálora;Matthew Moye;T. Brown;R. Lucas;C. Diekman;M. D. Belle
中科院分区：
文献类型：
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作者：
Beatriz Baño-Otálora;Matthew Moye;T. Brown;R. Lucas;C. Diekman;M. D. Belle
哺乳动物的每日或昼夜节律是由下丘脑视交叉上核（SCN）内的主生物钟精心安排的。在这里，基因表达、内在膜特性和突触通讯的细胞自主振荡塑造了 SCN 在昼夜节律中的电景观，使 SCN 神经元在白天明显比晚上更活跃。 SCN 的这一广为人知的生物电特征绝大多数是从对少数夜间活动的啮齿动物进行的研究中得出的。因此，我们首次研究了昼间哺乳动物 SCN 神经元的自发电活动和诱发电活动。为此，我们在白天和晚上在昼行鼠类啮齿动物 Rhabdomys pumilio 制备的脑切片中测量了单个 SCN 神经元的电活动，然后开发了尖端的数据同化和数学建模方法来揭示潜在的离子机制。我们发现 R. pumilio SCN 神经元在白天比晚上更兴奋，重现了先前在夜间啮齿动物中观察到的 SCN 神经元活动的典型模式。相比之下，R. pumilio 神经元的诱发活动包括显着的抑制反应，而夜间啮齿动物的 SCN 中不存在这种反应。我们的计算建模方法揭示了瞬时阈下 A 型钾通道是抑制反应的主要决定因素，并强调了这种离子机制在调节时钟神经元的兴奋性和优化 SCN 功能以适应 R. pumilio 的昼夜生态位方面的关键作用。
Daily or circadian rhythms in mammals are orchestrated by a master circadian clock within the hypothalamic suprachiasmatic nuclei (SCN). Here, cell-autonomous oscillations in gene expression, intrinsic membrane properties, and synaptic communication shape the electrical landscape of the SCN across the circadian day, rendering SCN neurons overtly more active during the day than at night. This well-accepted hallmark bioelectrical feature of the SCN has overwhelmingly emerged from studies performed on a small number of nocturnal rodent species. Therefore, for the first time, we investigate the spontaneous and evoked electrical activity of SCN neurons in a diurnal mammal. To this end, we measured the electrical activity of individual SCN neurons during the day and at night in brain slices prepared from the diurnal murid rodent Rhabdomys pumilio and then developed cutting-edge data assimilation and mathematical modelling approaches to uncover the underlying ionic mechanisms. We find that R. pumilio SCN neurons were more excited in the day than at night, recapitulating the prototypical pattern of SCN neuronal activity previously observed in nocturnal rodents. By contrast, the evoked activity of R. pumilio neurons included a prominent suppressive response that is not present in the SCN of nocturnal rodents. Our computational modelling approaches reveal transient subthreshold A-type potassium channels as the primary determinant of the suppressive response and highlight a key role for this ionic mechanism in tuning excitability of clock neurons and optimising SCN function to accommodate R. pumilio’s diurnal niche.