title: Calcium response to retinohypothalamic tract synaptic transmission in suprachiasmatic nucleus neurons.
abstract: Glutamate released from retinohypothalamic tract (RHT) synapses with suprachiasmatic nucleus (SCN) neurons induces phase changes in the circadian clock presumably by using Ca2+ as a second messenger. We used electrophysiological and Ca2+ imaging techniques to simultaneously record changes in the membrane potential and intracellular calcium concentration ([Ca2+]i) in SCN neurons after stimulation of the RHT at physiologically relevant frequencies. Stimulation of the RHT sufficient to generate an EPSP did not produce detectable changes in [Ca2+]i, whereas EPSP-induced action potentials evoked an increase in [Ca2+]i, suggesting that the change in postsynaptic somatic [Ca2+]i produced by synaptically activated glutamate receptors was the result of membrane depolarization activating voltage-dependent Ca2+ channels. The magnitude of the Ca2+ response was dependent on the RHT stimulation frequency and duration, and on the SCN neuron action potential frequency. Membrane depolarization-induced changes in [Ca2+]i were larger and decayed more quickly in the dendrites than in the soma and were attenuated by nimodipine, suggesting a compartmentalization of Ca2+ signaling and a contribution of L-type Ca2+ channels. RHT stimulation at frequencies that mimicked the output of light-sensitive retinal ganglion cells (RGCs) evoked [Ca2+]i transients in SCN neurons via membrane depolarization and activation of voltage-dependent Ca2+ channels. These data suggest that for Ca2+ to induce phase advances or delays, light-induced signaling from RGCs must augment the underlying oscillatory somatic [Ca2+]i by evoking postsynaptic action potentials in SCN neurons during a period of slow spontaneous firing such as occurs during nighttime.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon 97239, USA. irwinr@ohsu.edu
authors.forename: Robert P
authors.initials: RP
authors.lastname: Irwin
authors.forename: Charles N
authors.initials: CN
authors.lastname: Allen
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*