title: Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated inhibition of GABA release from cholecystokinin expressing basket cells.
abstract: Cholecystokinin (CCK) is an abundant neuropeptide involved in normal behaviour and pathophysiological conditions. Recently, CCK was shown to act as a molecular switch for perisomatic inhibition in the hippocampus, by directly depolarizing parvalbumin expressing (PV+) basket cells while indirectly depressing GABA release from CCK expressing (CCK+) basket cells. However, whether these two CCK-mediated effects are causally related is controversial, with one hypothesis proposing that the CCK-induced firing of PV+ basket cells increases the release of GABA, which, in turn, heterosynaptically inhibits GABA release from neighbouring CCK+ basket cell terminals through presynaptic GABAB receptors. Our present data from paired recording experiments from presynaptic basket cells and postsynaptic CA1 pyramidal cells in acute rat brain slices show that the P/Q Ca2+ channel antagonist agatoxin TK (250 nm) abolished GABA release from PV+ basket cells, but it had no effect on the CCK-induced depression of GABA release from CCK+ basket cells. Furthermore, CCK decreased GABA release from CCK+ basket cells even in the presence of the GABAB receptor antagonist CGP55845 (2 μm). In contrast, cannabinoid type-1 (CB1) receptor blockade with AM251 (10 μm) prevented the action of CCK on GABA release both from CCK+ basket cells and dendritically projecting, CCK+ Schaffer collateral-associated interneurons. These results demonstrate that CCK-mediated inhibition of GABA release from CCK+ cells requires no cross-talk between PV+ and CCK+ synapses, but that it critically depends on CB1 receptor-mediated endocannabinoid signalling at both perisomatic and dendritic inputs.
authors.affiliation: Department of Anatomy and Neurobiology, UC Irvine, Irvine, CA 92697-1280, USA. sanghun.lee@uci.edu
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002766:Cholecystokinin / Q000096:biosynthesis / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D018756:GABA Antagonists; D043884:Receptor, Cannabinoid, CB1; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin