title: Cannabinoids attenuate hippocampal γ oscillations by suppressing excitatory synaptic input onto CA3 pyramidal neurons and fast spiking basket cells.
abstract: CB(1) cannabinoid receptor (CB(1)R) activation by exogenous ligands can impair memory processes, which critically depend on synchronous neuronal activities that are temporarily structured by oscillations. In this study, we aimed to reveal the mechanisms underlying the cannabinoid-induced decrease in gamma oscillations. We first verified that cannabinoids (CP55,940 and WIN55,212-2) readily suppressed carbachol-induced gamma oscillations in the CA3 region of hippocampal slices via activation of CB(1)Rs. The cannabinoid-induced decrease in the peak power of oscillations was accompanied by reduced and less precise firing activity in CA3 pyramidal cells and fast spiking basket cells. By examining the cannabinoid sensitivity of synaptic inputs we found that the amplitude of evoked excitatory postsynaptic currents was significantly suppressed upon CB(1)R activation in both CA3 pyramidal cells and fast spiking basket cells. In contrast, evoked inhibitory postsynaptic currents in CA3 pyramidal cells were unaltered. Furthermore, we observed that a CB(1)R agonist-induced decrease in the oscillation power at the beginning of the drug application was accompanied primarily by the reduced discharge of fast spiking basket cells, while pyramidal cell firing was unaltered. This result implies that the dampening of cholinergically induced gamma oscillations in the hippocampus by cannabinoids can be explained by a reduced excitatory input predominantly onto fast spiking basket cells, which leads to a reduction in neuronal firing frequency and precision, and thus to smaller field potentials. In addition, we uncovered that the spontaneously occurring sharp wave-ripple activities in hippocampal slices could also be suppressed by CB(1)R activation suggesting that cannabinoids profoundly reduce the intrinsically generated oscillatory activities at distinct frequencies in CA3 networks by reducing synaptic neurotransmission.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Noémi
authors.initials: N
authors.lastname: Holderith
authors.forename: Beáta
authors.initials: B
authors.lastname: Németh
authors.forename: Orsolya I
authors.initials: OI
authors.lastname: Papp
authors.forename: Judit M
authors.initials: JM
authors.lastname: Veres
authors.forename: Gergo A
authors.initials: GA
authors.lastname: Nagy
authors.forename: Norbert
authors.initials: N
authors.lastname: Hájos
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D002186:Cannabinoids / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D018679:Cholinergic Agonists; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D002217:Carbachol