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bioRxiv · 10.1101/2025.03.29.646123

Photoperiodic Regulation of SK Channels in Dorsal Raphe Serotonin Neurons

Giannoni Guzman, M. A.·Zepeda, J. C.·Kamitakahara, A.·Magalong, V.·Levitt, P.·Grueter, B.·McMahon, D. G.
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Abstract

Day length, or seasonal photoperiod, shapes mood and affective behaviors but the neural mechanisms underlying these effects are still being defined. Serotonin neurons of the dorsal raphe nucleus (DRN) are critical regulators of affective behaviors and photoperiod modulates their excitability and ongoing activity. Here, we investigated the influence of seasonal photoperiod on the function and expression of small conductance calcium-activated potassium (SK) channels which mediate the afterhyperpolarizing potential (AHP) in dorsal raphe serotonin neurons. Building on previous work demonstrating that photoperiod modulates serotonergic excitability and behavior, we hypothesized that day length influences SK channel activity, thereby contributing to differences in neuronal excitability observed between Long, Equinox, and Short photoperiod conditions. Using multi-electrode array recording of DRN slices we found a significant dose-dependent increase in spike rate to the application of the SK channel inhibitor apamin, indicating that SK channels indeed influence the spike rate of dorsal raphe serotonin neurons. In addition, DRN neurons in slices from Long photoperiod mice exhibited less pronounced responses to apamin relative to those from Short photoperiod mice, suggesting reduced function or expression of SK channels in Long photoperiod. Indeed, whole-cell recordings demonstrated that SK channel-mediated AHP currents were reduced in Long photoperiod mice. However, there were no significant differences in expression levels of the SK3 subunit (Kcnn3) in DRN serotonin neurons across photoperiod conditions as determined by single molecule fluorescence in situ hybridization. Overall, these findings indicate that photoperiod modulates SK channel function in DRN serotonin neurons likely at a post-transcriptional level. This study advances our understanding of how seasonal cues influence intrinsic neuronal properties and provides a mechanistic link between photoperiod, serotonergic excitability, and mood-related behaviors. The identification of SK channels as modulators of photoperiodic effects may offer novel therapeutic targets for mood disorders associated with dysregulated serotonin signaling.

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Giannoni Guzman, M. A., Zepeda, J. C., Kamitakahara, A., Magalong, V., Levitt, P., Grueter, B., McMahon, D. G.. 2025-04-01. Photoperiodic Regulation of SK Channels in Dorsal Raphe Serotonin Neurons. https://doi.org/10.1101/2025.03.29.646123

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