Deng, Pan-Yue Xiao, Zhaoyang Jha, Archana Ramonet, David Matsui, Toshimitsu Leitges, Michael Shin, Hee-Sup Porter, James E. Geiger, Jonathan D. Lei, Saobo 2024-01-20T19:32:10Z 2024-01-20T19:32:10Z 2021-09-02 2010-04-14 0270-6474 https://pubs.kist.re.kr/handle/201004/131543 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 Ca2+ release and protein kinase C gamma. 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. English SOC NEUROSCIENCE INHIBITS NEURONAL EXCITABILITY RAT HIPPOCAMPAL-NEURONS ENTORHINAL CORTEX DENTATE GYRUS IN-VIVO PYRAMIDAL NEURONS GABA RELEASE K+ CHANNELS GABAERGIC TRANSMISSION RECEPTOR LIGANDS Cholecystokinin Facilitates Glutamate Release by Increasing the Number of Readily Releasable Vesicles and Releasing Probability Article 10.1523/JNEUROSCI.5711-09.2010 1 JOURNAL OF NEUROSCIENCE, v.30, no.15, pp.5136 - 5148 JOURNAL OF NEUROSCIENCE 30 15 5136 5148 scie scopus 000276685100002 2-s2.0-77950968404 Neurosciences Neurosciences & Neurology Article INHIBITS NEURONAL EXCITABILITY RAT HIPPOCAMPAL-NEURONS ENTORHINAL CORTEX DENTATE GYRUS IN-VIVO PYRAMIDAL NEURONS GABA RELEASE K+ CHANNELS GABAERGIC TRANSMISSION RECEPTOR LIGANDS