title: Mechanism of bilateral communication in the suprachiasmatic nucleus.
abstract: The central circadian pacemaker of the suprachiasmatic nuclei (SCN) is a bilaterally symmetrical structure. Little is known about the physiological mechanisms underlying communication between the left and right SCN and yet the degree of synchronization between SCN neurons can have a critical impact on the properties of the circadian system. In this study, we used electrophysiological tools and calcium (Ca(2+) ) imaging to examine the mechanisms underlying bilateral signaling in mouse SCN. Electrical stimulation of one SCN produced responses in the contralateral SCN with a short delay (approximately 5 ms) and Ca(2+) -dependence that are consistent with action potential-mediated chemical synaptic transmission. Patch-clamp recordings of stimulated cells revealed excitatory postsynaptic inward-currents (EPSCs), which were sufficient in magnitude to elicit action potentials. Electrical stimulation evoked tetrodotoxin-dependent Ca(2+) transients in about 30% of all contralateral SCN neurons recorded. The responding neurons were widely distributed within the SCN with a highest density in the posterior SCN. EPSCs and Ca(2+) responses were significantly reduced after application of a glutamate receptor antagonist. Application of antagonists for receptors of other candidate transmitters inhibited the Ca(2+) responses in some of the cells but overall the impact of these antagonists was variable. In a functional assay, electrical stimulation of the SCN produced phase shifts in the circadian rhythm in the frequency of multiunit activity rhythm in the contralateral SCN. These phase shifts were blocked by a glutamate receptor antagonist. Taken together, these results implicate glutamate as a transmitter required for communication between the left and right SCN.
authors: Laboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, LUMC PZ S5-P, PO 9600, 2300 RC, Leiden, The Netherlands. S.Michel@lumc.nl
authors: Stephan
authors: S
authors: Michel
authors: Roger
authors: R
authors: Marek
authors: Henk T
authors: HT
authors: Vanderleest
authors: Mariska J
authors: MJ
authors: Vansteensel
authors: William J
authors: WJ
authors: Schwartz
authors: Christopher S
authors: CS
authors: Colwell
authors: Johanna H
authors: JH
authors: Meijer
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002940:Circadian Rhythm; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D007839:Functional Laterality; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011930:Reaction Time; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D002118:Calcium