PT  - JOURNAL ARTICLE
AU  - Pan-Yue Deng
AU  - Zhaoyang Xiao
AU  - Archana Jha
AU  - David Ramonet
AU  - Toshimitsu Matsui
AU  - Michael Leitges
AU  - Hee-Sup Shin
AU  - James E. Porter
AU  - Jonathan D. Geiger
AU  - Saobo Lei
TI  - Cholecystokinin Facilitates Glutamate Release by Increasing the Number of Readily Releasable Vesicles and Releasing Probability
AID  - 10.1523/JNEUROSCI.5711-09.2010
DP  - 2010 Apr 14
TA  - The Journal of Neuroscience
PG  - 5136--5148
VI  - 30
IP  - 15
4099  - http://www.jneurosci.org/content/30/15/5136.short
4100  - http://www.jneurosci.org/content/30/15/5136.full
SO  - J. Neurosci.2010 Apr 14; 30
AB  - 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 Cγ. 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.