Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse (Review) Review Article

Author(s): Hefft, Stefan; Jonas, Peter
Title: Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse (Review)
Abstract: Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca(2+) channels mediate release at PV interneuron synapses. Effects of Ca(2+) chelators suggest that both a long-lasting presynaptic Ca(2+) transient and a large distance between Ca(2+) source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.
Keywords: Animals; Time Factors; Rats; Electric Stimulation; Calcium Channel Blockers/pharmacology; Chelating Agents/pharmacology; Egtazic Acid/analogs & derivatives/pharmacology; Hippocampus/cytology; Rats, Wistar; Synapses/drug effects/physiology; Action Potentials/physiology; gamma-Aminobutyric Acid/metabolism; Axons/metabolism; Cholecystokinin/metabolism/pharmacology; Dose-Response Relationship, Radiation; Immunohistochemistry/methods; Parvalbumins/metabolism/pharmacology; Patch-Clamp Techniques/methods; Reaction Time/physiology/radiation effects; Spider Venoms/pharmacology; Statistics, Nonparametric; omega-Conotoxins/pharmacology; Interneurons/physiology; Neural Inhibition/drug effects/physiology; Neurons/drug effects/metabolism
Publication Title: Nature Neuroscience
Volume: 8
Issue 10
ISBN: 1546-1726
Publisher: Nature Publishing Group  
Publication Place: United States
Date Published: 2005-01-01
Start Page: 1319
End Page: 28
DOI: 10.1038/nn1542
Open access: no