title: Cholecystokinin facilitates glutamate release by increasing the number of readily releasable vesicles and releasing probability.
abstract: Cholecystokinin (CCK), a neuropeptide originally discovered in the gastrointestinal tract, is abundantly distributed in the mammalian brains including the hippocampus. Whereas CCK has been shown to increase glutamate concentration in the perfusate of hippocampal slices and in purified rat hippocampal synaptosomes, the cellular and molecular mechanisms whereby CCK modulates glutamatergic function remain unexplored. Here, we examined the effects of CCK on glutamatergic transmission in the hippocampus using whole-cell recordings from hippocampal slices. Application of CCK increased AMPA receptor-mediated EPSCs at perforant path-dentate gyrus granule cell, CA3-CA3 and Schaffer collateral-CA1 synapses without effects at mossy fiber-CA3 synapses. CCK-induced increases in AMPA EPSCs were mediated by CCK-2 receptors and were not modulated developmentally and transcriptionally. CCK reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that CCK facilitates presynaptic glutamate release. CCK increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. CCK-mediated increases in glutamate release required the functions of phospholipase C, intracellular Ca(2+) release and protein kinase Cgamma. CCK released endogenously from hippocampal interneurons facilitated glutamatergic transmission. Our results provide a cellular and molecular mechanism to explain the roles of CCK in the brain.
authors.affiliation: Department of Pharmacology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota 58203, USA.
authors.forename: Pan-Yue
authors.initials: PY
authors.lastname: Deng
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Xiao
authors.forename: Archana
authors.initials: A
authors.lastname: Jha
authors.forename: David
authors.initials: D
authors.lastname: Ramonet
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: James E
authors.initials: JE
authors.lastname: Porter
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Geiger
authors.forename: Saobo
authors.initials: S
authors.lastname: Lei
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002766:Cholecystokinin / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D017729:Presynaptic Terminals / Q000502:physiology; D011336:Probability; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D043887:Receptor, Cholecystokinin B; D018091:Receptors, AMPA; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; C087857:protein kinase C gamma; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium
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