Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 43, Pages 11748-11757Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1840-07.2007
Keywords
circadian rhythm; suprachiasmatic nucleus; action potential; retinal ganglion cells; synaptic transmission; calcium
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Funding
- NIGMS NIH HHS [R01 GM096972] Funding Source: Medline
- NIMH NIH HHS [R01 MH070922, MH 70922] Funding Source: Medline
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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 Ca(2+)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 fromRGCsmust 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. Key words: circadian rhythm; suprachiasmatic nucleus; action potential; retinal ganglion cells; synaptic transmission; calcium
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