title: Cholecystokinin inhibits endocannabinoid-sensitive hippocampal IPSPs and stimulates others.
abstract: Cholecystokinin (CCK) is the most abundant neuropeptide in the central nervous system. In the hippocampal CA1 region, CCK is co-localized with GABA in a subset of interneurons that synapse on pyramidal cell somata and apical dendrites. CCK-containing interneurons also uniquely express a high level of the cannabinoid receptor, CB(1), and mediate the retrograde signaling process called DSI. Reported effects of CCK on inhibitory post-synaptic potentials (IPSPs) in hippocampus are inconsistent, and include both increases and decreases in activity. Hippocampal interneurons are very heterogeneous, and these results could be reconciled if CCK affected different interneurons in different ways. To test this prediction, we used sharp microelectrode recordings from pyramidal cells with ionotropic glutamate receptors blocked, and investigated the effects of CCK on pharmacologically distinct groups of IPSPs during long-term recordings. We find that CCK, acting via the CCK(2) receptor, increases some IPSPs and decreases others, and most significantly, that the affected IPSPs can be classified into two groups by their pharmacological properties. IPSPs that are increased by carbachol (CCh-sIPSPs), are depressed by CCK, omega-conotoxin GVIA, and endocannabinoids. IPSPs that are enhanced by CCK (CCK-sIPSPs) are blocked by omega-agatoxin IVA, and are unaffected by carbachol or endocannabinoids. Interestingly, a CCK(2) antagonist enhances CCh-sIPSPs, suggesting normally they may be partially suppressed by endogenous CCK. In summary, our data are compatible with the hypothesis that CCK has opposite actions on sIPSPs that originate from functionally distinct interneurons.
authors: Department of Physiology, Program in Neuroscience, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
authors: Miranda A
authors: MA
authors: Karson
authors: Kevin C
authors: KC
authors: Whittington
authors: Bradley E
authors: BE
authors: Alger
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D063388:Endocannabinoids; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D063385:Cannabinoid Receptor Modulators; D018679:Cholinergic Agonists; D063388:Endocannabinoids; D013779:Tetrodotoxin; D002217:Carbachol; D002766:Cholecystokinin
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