title: Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse.
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.
authors.affiliation: Physiologisches Institut der Universität Freiburg, Hermann-Herder-Str. 7, D-79104 Freiburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hefft
authors.forename: Peter
authors.initials: P
authors.lastname: Jonas
mesh_terms: D000200:Action Potentials / Q000502:physiology; D060848:Agatoxins; D000818:Animals; D001369:Axons / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000502:physiology / Q000528:radiation effects; D013111:Spider Venoms / Q000494:pharmacology; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D020960:omega-Conotoxins / Q000494:pharmacology
chemical_list: D060848:Agatoxins; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D010320:Parvalbumins; D013111:Spider Venoms; D020960:omega-Conotoxins; C060465:omega-agatoxin I; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; C046770:EGTA acetoxymethyl ester