GABAergic signaling induces divergent neuronal Ca2+ responses in the suprachiasmatic nucleus network.
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 Ca(2+) imaging techniques to record changes in the intracellular calcium concentration ([Ca(2+)](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 Ca(2+) 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 [Ca(2+)](i). Application of the GABA(A) receptor antagonist gabazine induced changes in baseline [Ca(2+)](i) in a direction opposite to that evoked by GABA, and similarly altered the RHT stimulation-induced Ca(2+) response. GABA application induced Ca(2+) 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 [Ca(2+)](i). These results suggest that physiological GABA induces opposing effects on [Ca(2+)](i) based on the chloride equilibrium potential, and may play an important role in neuronal Ca(2+) balance, synchronization and modulation of light input signaling in the SCN network.
Irwin
Robert P
RP
Center for Research on Occupational and Environmental Toxicology (CROET), Oregon Health & Science University, Portland, OR 97239, USA. irwinr@ohsu.edu
Allen
Charles N
CN
D000818:Animals; D019540:Area Under Curve; D001703:Biophysics / Q000379:methods; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013493:Suprachiasmatic Nucleus / Q000166:cytology* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018682:GABA Agents; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D002118:Calcium