title: Asynchronous transmitter release from cholecystokinin-containing inhibitory interneurons is widespread and target-cell independent.
abstract: Neurotransmitter release at most central synapses is synchronized to the timing of presynaptic action potentials. Here, we show that three classes of depolarization-induced suppression of inhibition-expressing, cholecystokinin (CCK)-containing, hippocampal interneurons show highly asynchronous release in response to trains of action potentials. This asynchrony is correlated to the class of presynaptic interneuron but is unrelated to their postsynaptic cell target. Asynchronous and synchronous release from CCK-containing interneurons show a slightly different calcium dependence, such that the proportion of asynchronous release increases with external calcium concentration, possibly suggesting that the modes of release are mediated by different calcium sensors. Asynchronous IPSCs include very large (up to 500 pA/7nS) amplitude events, which persist in low extracellular calcium and strontium, showing that they result from quantal transmitter release at single release sites. Finally, we show that asynchronous release is prominent in response to trains of presynaptic spikes that mimic natural activity of CCK-containing interneurons. That asynchronous release from CCK-containing interneurons is a widespread phenomenon indicates a fundamental role for these cells within the hippocampal network that is distinct from the phasic inhibition provided by parvalbumin-containing interneurons.
authors.affiliation: Program in Developmental Neuroscience, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. dawmicha@mail.nih.gov
authors.forename: Michael I
authors.initials: MI
authors.lastname: Daw
authors.forename: Ludovic
authors.initials: L
authors.lastname: Tricoire
authors.forename: Ferenc
authors.initials: F
authors.lastname: Erdelyi
authors.forename: Gabor
authors.initials: G
authors.lastname: Szabo
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002766:Cholecystokinin / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000502:physiology; D055366:Synaptic Potentials / Q000235:genetics / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D002766:Cholecystokinin; D002118:Calcium