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.
College or School
School of Medicine
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Supplemental Associated Link
Gonzalez JC, Lee H, Vincent AM, Hill AL, Goode LK, King GD, Gamble KL, Wadiche JI, Overstreet-Wadiche L. Circadian regulation of dentate gyrus excitability mediated by G-protein signaling. Cell Rep. 2023 Feb 6;42(2):112039. doi: 10.1016/j.celrep.2023.112039. Epub ahead of print. PMID: 36749664.