GABAergic signaling induces divergent neuronal Ca2+ responses
in the suprachiasmatic nucleus network

Abstract

Intercellular communication between γ-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. GABAA and GABAB
receptor agonists and antagonists were used to evaluate components of the GABA-induced
changes in [Ca2+]i. Application of the GABAA 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.