Melatonin Enhances Sleep via MT1-Driven Activation of Slo1 in Suprachiasmatic Nucleus Neurons
Wang, Z.-W.; Vedantham, K.; Ahmad, A.; Niu, L.-G.; Shui, Y.; Lemtiri-Chlieh, F.; Kaback, D.; Ma, X.-M.; Yee, S.-P.
Show abstract
Melatonin promotes sleep through mechanisms that have remained elusive. Here, we identify a molecular pathway by which melatonin promotes sleep by activating BK channels (Slo1) via MT1 receptors in the suprachiasmatic nucleus (SCN), the brains master circadian clock. In melatonin-proficient CBA/CaJ mice, knockout of either MT1 or Slo1 reduces REM and NREM sleep during the rest phase (daytime), accompanied by prolonged action potentials and diminished afterhyperpolarization in SCN neurons. These electrophysiological and behavioral changes are minimal during the active phase (nighttime). Strikingly, Slo1 expression in the SCN peaks during the daytime, contrary to previous reports, but aligning with its sleep-promoting function. Slo1, but not MT1, deletion also triggers spontaneous seizures, highlighting broader functions beyond circadian control. Structural mapping identifies critical domains mediating MT1-Slo1 coupling. Together, these findings position the MT1-Slo1 signaling axis as a core circadian mechanism linking melatonin to sleep regulation and a potential therapeutic target for sleep disorders.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Sleep need driven oscillation of glutamatergic synaptic phenotype 95%
- BK channel properties correlate with neurobehavioral severity in three KCNMA1-linked channelopathy mouse models 94%
- Coupling of Slack and NaV1.6 sensitizes Slack to quinidine blockade and guides anti-seizure strategy development 94%
Similar papers in this journal
- Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism 95%
- Sensory regulation of absence seizures in a mouse model of Gnb1 encephalopathy 94%
- Context-dependent NMDA receptor dysfunction predicts seizure treatment in mice with human GluN1 variant 94%
Similar papers in this journal
- Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture 95%
- Neuronal feedback loop in the suprachiasmatic nucleus generates robust circadian rhythms 95%
- Reassessing the validity of slow-wave dynamics as a proxy for NREM sleep homeostasis 94%
Similar papers in this journal
- Disease-causing Slack potassium channel mutations produce opposite effects on excitability of excitatory and inhibitory neurons 95%
- Developmentally-regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome 95%
- Severe deficiency of voltage-gated sodium channel NaV1.2 elevates neuronal excitability in adult mice 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.