Calcium response to retinohypothalamic tract synaptic transmission in suprachiasmatic nucleus neurons.
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.
Irwin
Robert P
RP
Center for Research on Occupational and Environmental Toxicology, Oregon Health & Science University, Portland, Oregon 97239, USA. irwinr@ohsu.edu
Allen
Charles N
CN
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*