title: Presynaptic, activity-dependent modulation of cannabinoid type 1 receptor-mediated inhibition of GABA release.
abstract: Endocannabinoid signaling couples activity-dependent rises in postsynaptic Ca2+ levels to decreased presynaptic GABA release. Here, we present evidence from paired recording experiments that cannabinoid-mediated inhibition of GABA release depends on the firing rates of the presynaptic interneurons. Low-frequency action potentials in post hoc identified cholecystokinin-positive CA1 basket cells elicited IPSCs in the postsynaptic pyramidal cells that, as expected, were fully abolished by the exogenous application of the cannabinoid receptor agonist WIN55,212-2 [R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate] at 5 microM. However, the presynaptic basket cells recovered from the cannabinoid agonist-induced inhibition of GABA release when the presynaptic firing rate was increased to > or =20 Hz. Pharmacological experiments showed that the recovered transmission was exclusively dependent on presynaptic N-type Ca2+ channels. Furthermore, the increased presynaptic firing could also overcome even complete depolarization-induced suppression of inhibition, indicating that the magnitude of DSI markedly depends on the activity levels of basket cells. These results reveal a new locus of activity-dependent modulation for endocannabinoid signaling and suggest that endocannabinoid-mediated inhibition of GABA release may differ in distinct behavioral states.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, California 92697-1280, USA. cfoldy@uci.edu
authors.forename: Csaba
authors.initials: C
authors.lastname: Földy
authors.forename: Axel
authors.initials: A
authors.lastname: Neu
authors.forename: Mathew V
authors.initials: MV
authors.lastname: Jones
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
mesh_terms: D000200:Action Potentials; D000818:Animals; D048588:Benzoxazines; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology; D002766:Cholecystokinin / Q000032:analysis; D005071:Evoked Potentials; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000502:physiology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009433:Neural Inhibition; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D048588:Benzoxazines; D020864:Calcium Channels, N-Type; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; D005680:gamma-Aminobutyric Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D002766:Cholecystokinin