SIK3 and Wnk converge on Fray to regulate glial K+ buffering and seizure susceptibility.

Glial cells play a critical role in maintaining homeostatic ion concentration gradients. Salt-inducible kinase 3 (SIK3) regulates a gene expression program that controls K+ buffering in glia, and upregulation of this pathway suppresses seizure behavior in the eag, Shaker hyperexcitability mutant. Here we show that boosting the glial SIK3 K+ buffering pathway suppresses seizures in three additional molecularly diverse hyperexcitable mutants, highlighting the therapeutic potential of upregulating glial K+ buffering.

Bidirectional regulation of glial potassium buffering - glioprotection versus neuroprotection.

Glia modulate neuronal excitability and seizure sensitivity by maintaining potassium and water homeostasis. A salt inducible kinase 3 (SIK3)-regulated gene expression program controls the glial capacity to buffer K and water in , however upstream regulatory mechanisms are unknown. Here, we identify an octopaminergic circuit linking neuronal activity to glial ion and water buffering.

SCN VIP Neurons Are Essential for Normal Light-Mediated Resetting of the Circadian System.

The suprachiasmatic nucleus (SCN) synchronizes circadian rhythms in behavior and physiology to the external light cycle, but the mechanisms by which this occurs are unclear. As the neuropeptide vasoactive intestinal peptide (VIP) is important for circadian light responses, we tested the hypothesis that rhythmic VIP-producing SCN neurons mediate circadian light responses in male and female mice. Using fiber photometry over multiple days, we found daily rhythms in spontaneous calcium events of SCN VIP neurons that peaked during the subjective day and were disrupted by constant light.