Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 30, Issue 8, Pages 1462-1475Publisher
WILEY-BLACKWELL PUBLISHING, INC
DOI: 10.1111/j.1460-9568.2009.06944.x
Keywords
chloride cotransporter; circadian rhythm; retinohypothalamic tract; synaptic transmission
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Funding
- [MH 70922]
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Intercellular communication between gamma-aminobutyric acid (GABA)ergic suprachiasmatic nucleus (SCN) neurons facilitates light-induced phase changes and synchronization of individual neural oscillators within the SCN network. We used ratiometric Ca2+ imaging techniques to record changes in the intracellular calcium concentration ([Ca2+](i)) to study the role of GABA in interneuronal communication and the response of the SCN neuronal network to optic nerve stimulations that mimic entraining light signals. Stimulation of the retinohypothalamic tract (RHT) evoked divergent Ca2+ responses in neurons that varied regionally within the SCN with a pattern that correlated with those evoked by pharmacological GABA applications. GABA(A) and GABA(B) receptor agonists and antagonists were used to evaluate components of the GABA-induced changes in [Ca2+](i). Application of the GABA(A) receptor antagonist gabazine induced changes in baseline [Ca2+](i) in a direction opposite to that evoked by GABA, and similarly altered the RHT stimulation-induced Ca2+ response. GABA application induced Ca2+ responses varied in time and region within the SCN network. The NKCC1 cotransporter blocker, bumetanide, and L-type calcium channel blocker, nimodipine, attenuated the GABA-induced rise of [Ca2+](i). These results suggest that physiological GABA induces opposing effects on [Ca2+](i) based on the chloride equilibrium potential, and may play an important role in neuronal Ca2+ balance, synchronization and modulation of light input signaling in the SCN network.
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