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Circadian photoperiod alters TREK‐1 channel function and expression in dorsal raphe serotonergic neurons via melatonin receptor 1 signaling
Journal of Pineal Research ( IF 8.3 ) Pub Date : 2020-11-19 , DOI: 10.1111/jpi.12705
Manuel A Giannoni-Guzmán 1 , Anna Kamitakahara 2 , Valerie Magalong 2 , Pat Levitt 2 , Douglas G McMahon 1, 3
Affiliation  

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.

中文翻译:

昼夜光周期通过褪黑激素受体 1 信号改变中缝背血清素能神经元中 TREK-1 通道的功能和表达

季节性白天长度与情绪障碍的患病率有关,然而,这种关系背后的机制仍然未知。我们实验室以前的工作表明,发育性暴露于季节性光周期对小鼠中缝背侧血清素能神经元的活动、它们的内在电特性以及抑郁和焦虑相关的行为具有持久的影响。在这里,我们关注可能的离子机制,这些机制是观察到的血清素神经元电生理特性编程的基础,重点是双孔 K + 通道 TREK-1 和 TASK-1,它们设置静息膜电位和调节兴奋性。TREK-1的药理抑制显着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的放电率,这表明 TREK-1 功能在长光周期中降低。相比之下,TASK-1 的抑制导致所有光周期的放电率增加,这表明它有助于设置兴奋性,但不受光周期的调节。然后我们量化使用三标签 RNAscope 在背缝 5-HT 神经元中特异性地检测 Kcnk2 mRNA 水平。我们发现长光周期显着降低了共同表达Tph2Pet-1的血清素神经元中Kcnk2的水平。在褪黑激素 1 受体敲除 (MT-1KO) 小鼠中,光周期对 TREK-1 功能和表达的影响被阻断,这与之前的发现一致,即 MT-1 信号传导对于中缝背侧 5-HT 神经元的光周期编程是必需的。综上所述,这些结果表明,TREK-1 表达和功能的光周期调节在中缝背侧 5-HT 神经元的光周期编程中起着关键作用。
更新日期:2020-11-19
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