TASK-3 Two-Pore Potassium Channels drive neuronal excitability of the circadian clock and entrainment to challenging light environments

Abstract

The suprachiasmatic nucleus (SCN), the mammalian circadian clock, is a heterogenous structure made of several neuron types that generate a circadian electrical activity profile. However, it is unclear how such regulation in endogenous neuronal excitability is maintained. Background two-pore domain potassium channels (K2P), such as TASK-3, play an important role in inhibiting neuronal activity. Here, we utilize a TASK-3 KO mouse model to unravel the role played by this channel in SCN circadian neuronal regulation and behavioral photoentrainment. Our results reveal that TASK-3 is needed to adapt to challenging lighting conditions, such as those experienced through seasonal changes and jet lag. From our investigations this appears to be very distinct from pathways that drive acute, ‘one-off’ adjustments in clock phase, in response to single pulses of light. These findings provide crucial information on the intricate pathways linking clock output to behavioral adaptation to light-dark cycles.

Diverse genetic alteration dysregulates neuropeptide and intracellular signalling in the suprachiasmatic nuclei

“…Further, the enriched GO:MF terms for potassium channel activity highlights the possibility that control of neuronal firing is altered by dysregulation of gene expression, which could impede neuropeptide release in downstream targets of SCN efferents. Indeed, kcnk9 , which codes for a two‐pore domain potassium channel, TASK3, is implicated in multiple GO:MF terms at the night phase and available evidence indicates that in the absence of TASK3, ensemble SCN neuronal activity does not vary from day to night (Steponenaite et al, 2020).…”