Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock.
Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN), the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.
Department of Molecular & Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Sabra M
SM
Abbott
Jennifer M
JM
Arnold
Qing
Q
Chang
Hai
H
Miao
Nobutoshi
N
Ota
Christine
C
Cecala
Paul E
PE
Gold
Jonathan V
JV
Sweedler
Martha U
MU
Gillette
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D057906:Circadian Clocks / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology*; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D012890:Sleep / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
D018698:Glutamic Acid; D000109:Acetylcholine