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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 102/1/146    most recent 00130.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Hirasawa, H. Articles by Raviola, E. PubMed PubMed Citation Articles by Hirasawa, H. Articles by Raviola, E.

Extrasynaptic Release of GABA by Retinal Dopaminergic Neurons

Department of Neurobiology, Harvard Medical School, Boston, Massachusetts

Submitted 13 February 2009; accepted in final form 24 April 2009

GABA release by dopaminergic amacrine (DA) cells of the mouse retina was detected by measuring Cl^– currents generated by isolated perikarya in response to their own neurotransmitter. The possibility that the Cl^– currents were caused by GABA release from synaptic endings that had survived the dissociation of the retina was ruled out by examining confocal Z series of the surface of dissociated tyrosine hydroxylase-positive perikarya after staining with antibodies to preand postsynaptic markers. GABA release was caused by exocytosis because 1) the current events were transient on the millisecond time scale and thus resembled miniature synaptic currents; 2) they were abolished by treatment with a blocker of the vesicular proton pump, bafilomycin A1; and 3) their frequency was controlled by the intracellular Ca²⁺ concentration. Because DA cell perikarya do not contain presynaptic active zones, release was by necessity extrasynaptic. A range of depolarizing stimuli caused GABA exocytosis, showing that extrasynaptic release of GABA is controlled by DA cell electrical activity. With all modalities of stimulation, including long-lasting square pulses, segments of pacemaker activity delivered by the action-potential-clamp method and high-frequency trains of ramps, discharge of GABAergic currents exhibited considerable variability in latency and duration, suggesting that coupling between Ca²⁺ influx and transmitter exocytosis is extremely loose in comparison with the synapse. Paracrine signaling based on extrasynaptic release of GABA by DA cells and other GABAergic amacrines may participate in controlling the excitability of the neuronal processes that interact synaptically in the inner plexiform layer.