Circadian regulation of dentate gyrus excitability mediated by G-protein signaling

The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machin...

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Veröffentlicht in:Cell reports (Cambridge) 2023-02, Vol.42 (2), p.112039-112039, Article 112039
Hauptverfasser: Gonzalez, Jose Carlos, Lee, Haeun, Vincent, Angela M., Hill, Angela L., Goode, Lacy K., King, Gwendalyn D., Gamble, Karen L., Wadiche, Jacques I., Overstreet-Wadiche, Linda
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Sprache:eng
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Zusammenfassung:The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery, but whether these molecular programs generate oscillations of membrane properties is unclear. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-h oscillation that controls spiking probability. Diurnal changes in excitability are mediated by antiphase G-protein regulation of potassium and sodium currents that reduce excitability during the Light phase. Disruption of the circadian transcriptional machinery by conditional deletion of Bmal1 enhances excitability selectively during the Light phase by removing G-protein regulation. These results reveal that circadian transcriptional machinery regulates intrinsic excitability by coordinated regulation of ion channels by G-protein signaling, highlighting a potential novel mechanism of cell-autonomous oscillations. [Display omitted] •Dentate neurons exhibit a 24-h oscillation of intrinsic excitability and spiking•Low excitability during the Light phase results from inhibitory G-protein signaling•Conditional Bmal1 deletion increases excitability and spatial discrimination•Bmal1 deletion disrupts G-protein regulation of membrane leak currents Gonzalez et al. show that dentate gyrus neurons exhibit a 24-h cycle of intrinsic excitability and synaptic recruitment mediated by inhibitory G-protein regulation of membrane currents. The cycle of excitability is linked to the cell-intrinsic molecular clock transcriptional machinery, with low excitability during the Light phase.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2023.112039