title: Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release.
abstract: Cannabis consumption results in impaired learning. The proper synchronization of neuronal activity in the mammalian hippocampus gives rise to network rhythms that are implicated in memory formation. Here, we have studied the impact of cannabinoids on hippocampal sharp waves and associated ripple oscillations using field- and whole-cell voltage-clamp recordings. We demonstrate that the activation of cannabinoid receptor 1 suppresses sharp wave-ripples (SWRs) in mice in vivo and in vitro. This suppression was paralleled by a selective reduction of SWR-associated inward but not outward charge transfer, demonstrating an impairment of excitation due to cannabinoid exposure. Adenosine, a presynaptic modulator of glutamate release, mimicked and occluded the observed consequences of cannabinoids on SWRs. We conclude that inhibition of glutamatergic feed-forward excitation can explain cannabinoid-mediated disruption of SWRs and may account for cannabinoid-induced impairment of hippocampus-dependent memory.
authors.affiliation: Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany. nikolaus.maier@charite.de
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Maier
authors.forename: Genela
authors.initials: G
authors.lastname: Morris
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schuchmann
authors.forename: Tatiana
authors.initials: T
authors.lastname: Korotkova
authors.forename: Alexey
authors.initials: A
authors.lastname: Ponomarenko
authors.forename: Claudia
authors.initials: C
authors.lastname: Böhm
authors.forename: Christian
authors.initials: C
authors.lastname: Wozny
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D003511:Cyclohexanols / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism
chemical_list: D002186:Cannabinoids; D003511:Cyclohexanols; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol