title: Activation of glycine receptor phase-shifts the circadian rhythm in neuronal activity in the mouse suprachiasmatic nucleus.
abstract: In mammals, the master clock in the suprachiasmatic nucleus (SCN) of the hypothalamus is composed of numerous synchronized oscillating cells that drive daily behavioural and physiological processes. Several entrainment pathways, afferent inputs to the SCN with their neurotransmitter and neuromodulator systems, can reset the circadian system regularly and also modulate neuronal activity within the SCN. In the present study, we investigated the function of the inhibitory neurotransmitter glycine on neuronal activity in the mouse SCN and on resetting of the circadian clock. The effects of glycine on the electrical activity of SCN cells from C57Bl/6 mice were studied either by patch-clamp recordings from acute brain slices or by long-term recordings from organotypic brain slices using multi-microelectrode arrays(MEA). Voltage-clamp recordings confirmed the existence of glycine-induced, chloride-selective currents in SCN neurons. These currents were reversibly suppressed by strychnine, phenylbenzeneω-phosphono-α-amino acid (PMBA) or ginkgolide B, selective blockers of glycine receptors(GlyRs). Long-term recordings of the spontaneous activity of SCN neurons revealed that glycine application induces a phase advance during the subjective day and a phase delay during the early subjective night. Both effects were suppressed by strychnine or by PMBA. These results suggest that glycine is able to modulate circadian activity by acting directly on its specific receptors in SCN neurons.
authors.affiliation: Max-Planck-Institut für Hirnforschung, Deutschordenstr. 46, 60528 Frankfurt/Main, Germany.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mordel
authors.forename: Diana
authors.initials: D
authors.lastname: Karnas
authors.forename: Alexey
authors.initials: A
authors.lastname: Inyushkin
authors.forename: Etienne
authors.initials: E
authors.lastname: Challet
authors.forename: Paul
authors.initials: P
authors.lastname: Pévet
authors.forename: Hilmar
authors.initials: H
authors.lastname: Meissl
mesh_terms: D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008839:Microelectrodes; D009433:Neural Inhibition; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002712:Chlorides; D018691:Excitatory Amino Acid Antagonists; D018009:Receptors, Glycine; D005998:Glycine