Presynaptically Located CB1 Cannabinoid Receptors Regulate GABA Release from Axon Terminals of Specific Hippocampal Interneurons

摘要: To understand the functional significance and mechanisms of action in CNS endogenous exogenous cannabinoids, it is crucial to identify neural elements that serve as structural substrate these actions. We used a recently developed antibody against CB1 cannabinoid receptor study this question hippocampal networks. Interneurons with features typical basket cells showed selective, intense staining for all subfields layers. Most them (85.6%) contained cholecystokinin (CCK), which corresponded 96.9% CCK-positive interneurons, whereas only 4.6% parvalbumin (PV)-containing expressed CB1. Accordingly, electron microscopy revealed CB1-immunoreactive axon terminals CCK-containing surrounded somata proximal dendrites pyramidal neurons, PV-positive cell similar locations were negative The synthetic agonist WIN 55,212-2 (0.01–3 μm) reduced dose-dependently electrical field stimulation-induced [ 3 H]GABA release from superfused slices, an EC 50 value 0.041 μm. Inhibition GABA by was not mediated inhibition glutamatergic transmission because effect glutamate blockers AP5 CNQX. In contrast, antagonist SR 141716A (1 prevented effect, itself did change outflow H]GABA. These results suggest cannabinoid-mediated modulation interneuron networks operate largely via presynaptic receptors on CCK-immunoreactive terminals. Reduction likely mechanism both ligands interfere network oscillations associated cognitive functions.