GABA interacts with photic signaling in the suprachiasmatic nucleus to regulate circadian phase shifts

• Published in: Neuroscience Vol. 109; no. 4; pp. 773 - 778
• Main Authors: Mintz, E.M, Jasnow, A.M, Gillespie, C.F, Huhman, K.L, Albers, H.E
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2002; Elsevier
• Subjects: Animals; baclofen; Baclofen - pharmacology; Biological and medical sciences; Chronobiology; Circadian Rhythm - drug effects; Circadian Rhythm - physiology; Cricetinae; Excitatory Amino Acid Agonists - pharmacology; Fundamental and applied biological sciences. Psychology; GABA Agonists - pharmacology; GABA-A Receptor Agonists; GABA-B Receptor Agonists; gamma-Aminobutyric Acid - metabolism; glutamate; Glutamic Acid - metabolism; light pulse; Male; Mesocricetus; microinjection; Muscimol - pharmacology; N-methyl- D-aspartic acid; N-Methylaspartate - pharmacology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons - drug effects; Neurons - metabolism; Photic Stimulation; Receptors, GABA - drug effects; Receptors, GABA - metabolism; Receptors, GABA-A - metabolism; Receptors, GABA-B - metabolism; Suprachiasmatic Nucleus - cytology; Suprachiasmatic Nucleus - drug effects; Suprachiasmatic Nucleus - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; tetrodotoxin; Tetrodotoxin - pharmacology; Vertebrates: anatomy and physiology, studies on body, several organs or systems; TTX, tetrodotoxin; RHT, retinohypothalamic tract; light pulse; N-methyl- D-aspartic acid; NMDA, N-methyl- D-aspartic acid; CT, circadian time; microinjection; tetrodotoxin; NPY, neuropeptide Y; baclofen; glutamate; SCN, suprachiasmatic nucleus of the hypothalamus; Suprachiasmatic nucleus; Phase shift; Rodentia; Central nervous system; Biological rhythm; Hypothalamus; Circadian rhythm; Gabaergic receptor; Vertebrata; Mammalia; Neurotransmitter; GABA; Hamster; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(01)00519-X

Circadian rhythms of physiology and behavior in mammals are driven by a circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. The majority of neurons in the suprachiasmatic nucleus are GABAergic, and activation of GABA receptors in the suprachiasmatic nucleus can induce phase shifts of the circadian pacemaker both in vivo and in vitro. GABA also modulates the phase shifts induced by light in vivo, and photic information is thought to be conveyed to the suprachiasmatic nucleus by glutamate. In the present study, we examined the interactions between GABA receptor agonists, glutamate agonists, and light in hamsters in vivo. The GABA A receptor agonist muscimol and the GABA B receptor agonist baclofen were microinjected into the suprachiasmatic nucleus at circadian time 13.5 (early subjective night), followed immediately by a microinjection of N-methyl- D-aspartate (NMDA). Both muscimol and baclofen significantly reduced the phase shifting effects of NMDA. Further, coadministration of tetrodotoxin with baclofen did not alter the inhibition of NMDA by baclofen, suggesting a postsynaptic mechanism for the inhibition of NMDA-induced phase shifts by baclofen. Finally, the phase shifting effects of microinjection of muscimol into the suprachiasmatic nucleus during the subjective day were blocked by a subsequent light pulse. These data suggest that GABA regulates the phase of the circadian clock through both pre- and postsynaptic mechanisms.