Circadian control of membrane excitability in Drosophila melanogaster lateral ventral clock neurons
Circadian control of membrane excitability in Drosophila melanogaster lateral ventral clock neurons
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DOI：
10.1523/jneurosci.1503-08.2008
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发表时间：
2008-06-18
影响因子：
5.3
通讯作者：
Nitabach, Michael N.
中科院分区：
文献类型：
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作者：
Cao, Guan;Nitabach, Michael N.
果蝇的昼夜节律由包含约 150 个时钟神经元的神经回路控制。尽管人们对自主细胞振荡的机制了解很多，但细胞振荡与控制生理和行为节律的功能输出之间的联系却知之甚少。为了解决这个问题，我们对侧腹侧时钟神经元（LN（v）s）进行了全细胞膜片钳记录，包括大（1LN（v）s）和小LN（v）（sLN（v）s），在成年果蝇全脑外植体中进行原位记录。我们在> 50% 的 1LN(v) 中发现两种不同大小的动作电位 (AP) 自发放电，并确定大 AP 起源于同侧视叶，小 AP 起源于对侧。 1LN(v) 静息膜电位 (RMP)、自发 AP 放电率和膜电阻在 12 小时光照/黑暗条件 (LD) 中作为一天中时间的函数进行循环调节。随着时间从黎明到黄昏，1LN(v) RMP 变得更加超极化，同时自发 AP 放电率和膜电阻降低。从黄昏到黎明，1LN(v) RMP 变得更加去极化，自发 AP 放电率和膜电阻保持稳定。相反，昼夜节律缺陷 per(0) null 突变体 1LNv 膜兴奋性在 LD 中几乎恒定。在持续黑暗 (DD) 中超过 24 小时，野生型 1LN(v) 膜兴奋性不受周期性调节，尽管 RMP 逐渐变得稍微去极化。 sLN(v) RMP 在开灯时去极化程度最大，而 LD 的变化主要集中在关灯时。我们的结果表明，LNv 膜兴奋性通过昼夜节律时钟依赖性机制编码一天中的时间，并且可能在调节果蝇昼夜节律行为中发挥关键作用。
Drosophila circadian rhythms are controlled by a neural circuit containing similar to 150 clock neurons. Although much is known about mechanisms of autonomous cellular oscillation, the connection between cellular oscillation and functional outputs that control physiological and behavioral rhythms is poorly understood. To address this issue, we performed whole-cell patch-clamp recordings on lateral ventral clock neurons (LN(v)s), including large (1LN(v)s) and small LN(v)s (sLN(v)s), in situ in adult fly whole-brain explants. We found two distinct sizes of action potentials (APs) in > 50% of 1LN(v)s that fire APs spontaneously, and determined that large APs originate in the ipsilateral optic lobe and small APs in the contralateral. 1LN(v) resting membrane potential (RMP), spontaneous AP firing rate, and membrane resistance are cyclically regulated as a function of time of day in 12 h light/dark conditions (LD). 1LN(v) RMP becomes more hyperpolarized as time progresses from dawn to dusk with a concomitant decrease in spontaneous AP firing rate and membrane resistance. From dusk to dawn, 1LN(v) RMP becomes more depolarized, with spontaneous AP firing rate and membrane resistance remaining stable. In contrast, circadian defective per(0) null mutant 1LNv membrane excitability is nearly constant in LD. Over 24 h in constant darkness (DD), wild-type 1LN(v) membrane excitability is not cyclically regulated, although RMP gradually becomes slightly more depolarized. sLN(v) RMP is most depolarized around lights-on, with substantial variability centered around lights-off in LD. Our results indicate that LNv membrane excitability encodes time of day via a circadian clock-dependent mechanism, and likely plays a critical role in regulating Drosophila circadian behavior.