Circadian photoperiod alters TREK-1 channel function and expression in dorsal raphe serotonergic neurons via melatonin receptor 1 signaling.
Circadian photoperiod alters TREK-1 channel function and expression in dorsal raphe serotonergic neurons via melatonin receptor 1 signaling.
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昼夜光周期通过褪黑素受体1信号改变中缝背核神经元TREK-1通道功能和表达。
DOI：
10.1111/jpi.12705
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发表时间：
2021-03
影响因子：
10.3
通讯作者：
McMahon DG
中科院分区：
文献类型：
--
作者：
Giannoni-Guzmán MA;Kamitakahara A;Magalong V;Levitt P;McMahon DG
季节性白天长度与情绪障碍的患病率有关，然而，这种关系的机制仍然未知。我们实验室以前的工作已经表明，发育暴露于季节性光周期对小鼠中缝背核神经元的活性、其内在电特性以及抑郁和焦虑相关行为具有持久的影响。在这里，我们专注于可能的离子机制，所观察到的5-羟色胺神经元的电生理特性的编程的基础上，集中在双孔K +通道TREK-1和ASK-1，设置静息膜电位和调节兴奋性。TREK-1的药理学抑制显著增加了短光周期和春分光周期中的尖峰频率，但没有进一步提高长光周期小鼠切片中的放电率，表明TREK-1功能在长光周期中降低。与此相反，在所有的光周期中，抑制Task-I导致放电率的增加，这表明它有助于设置兴奋性，但不受光周期调节。然后，我们使用三标记RNAscope定量Kcnk 2 mRNA水平特异性中缝背核5-HT神经元。我们发现长光周期显着降低了共表达Tph 2和Pet-1的5-羟色胺神经元中Kcnk 2的水平。在褪黑素1受体敲除（MT-1 KO）小鼠中，光周期对TREK-1的功能和表达的影响被阻断，这与先前的发现一致，即MT-1信号传导对于中缝背核5-HT神经元的光周期编程是必需的。总之，这些结果表明，TREK-1的表达和功能的光周期调节在光周期编程中缝背核5-HT神经元的兴奋性中起着关键作用。
Seasonal day length has been linked to the prevalence of mood disorders, and however, the mechanisms underlying this relationship remain unknown. Previous work in our laboratory has shown that developmental exposure to seasonal photoperiods has enduring effects on the activity of mouse dorsal raphe serotonergic neurons, their intrinsic electrical properties, as well as on depression and anxiety-related behaviors. Here we focus on the possible ionic mechanisms that underlie the observed programming of the electrophysiological properties of serotonin neurons, focusing on the twin-pore K + channels TREK-1 and TASK-1 that set resting membrane potential and regulate excitability. Pharmacological inhibition of TREK-1 significantly increased spike frequency in Short and Equinox photoperiods, but did not further elevate the firing rate in slices from Long photoperiod mice, suggesting that TREK-1 function is reduced in Long photoperiods. In contrast, inhibition of TASK-1 resulted in increases in firing rates across all photoperiods, suggesting that it contributes to setting excitability, but is not regulated by photoperiod. We then quantified Kcnk2 mRNA levels specifically in dorsal raphe 5-HT neurons using triple-label RNAscope. We found that Long photoperiod significantly reduced levels of Kcnk2 in serotonin neurons co-expressing Tph2, and Pet-1. Photoperiodic effects on the function and expression of TREK-1 were blocked in melatonin 1 receptor knockout (MT-1KO) mice, consistent with previous findings that MT-1 signaling is necessary for photoperiodic programming of dorsal raphe 5-HT neurons. Taken together these results indicate that photoperiodic regulation of TREK-1 expression and function plays a key role in photoperiodic programming the excitability of dorsal raphe 5-HT neurons.
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影响因子：
5.3
作者：
Santi, CM;Cayabyab, FS;Snutch, TP
通讯作者：
Snutch, TP
影响因子：
5.6
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3.3
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通讯作者：
Andersen SL
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3.3
作者：
Aller, M. I.;Wisden, W.
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Wisden, W.