Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons

Citation
I. Katona et al., Presynaptically located CB1 cannabinoid receptors regulate GABA release from axon terminals of specific hippocampal interneurons, J NEUROSC, 19(11), 1999, pp. 4544-4558
Citations number
83
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
19
Issue
11
Year of publication
1999
Pages
4544 - 4558
Database
ISI
SICI code
0270-6474(19990601)19:11<4544:PLCCRR>2.0.ZU;2-W
Abstract
To understand the functional significance and mechanisms of action in the C NS of endogenous and exogenous cannabinoids, it is crucial to identify the neural elements that serve as the structural substrate of these actions. We used a recently developed antibody against the CB1 cannabinoid receptor to study this question in hippocampal networks. Interneurons with features ty pical of basket cells showed a selective, intense staining for CB1 in all h ippocampal subfields and layers. Most of them (85.6%) contained cholecystok inin (CCK), which corresponded to 96.9% of all CCK-positive interneurons, w hereas only 4.6% of the parvalbumin (PV)-containing basket cells expressed CB1. Accordingly, electron microscopy revealed that CB1-immunoreactive axon terminals of CCK-containing basket cells surrounded the somata and proxima l dendrites of pyramidal neurons, whereas PV-positive basket cell terminals in similar locations were negative for CB1. The synthetic cannabinoid agon ist WIN 55,212-2 (0.01-3 mu M) reduced dose-dependently the electrical fiel d stimulation-induced [H-3]GABA release from superfused hippocampal slices, with an EC,, value of 0.041 mu M. Inhibition of GABA release by WIN 55,212 -2 was not mediated by inhibition of glutamatergic transmission because the WIN 55,212-2 effect was not reduced by the glutamate blockers AP5 and CNQX . In contrast, the CB1 cannabinoid receptor antagonist SR 141716A (1 mu M) prevented this effect, whereas by itself it did not change the outflow of [ H-3]GABA. These results suggest that cannabinoid-mediated modulation of hippocampal i nterneuron networks operate largely via presynaptic receptors on CCK-immuno reactive basket cell terminals. Reduction of GABA release from these termin als is the likely mechanism by which both endogenous and exogenous CB1 liga nds interfere with hippocampal network oscillations and associated cognitiv e functions.