title: Weeding out bad waves: towards selective cannabinoid circuit control in epilepsy.
abstract: Endocannabinoids are lipid-derived messengers, and both their synthesis and breakdown are under tight spatiotemporal regulation. As retrograde signalling molecules, endocannabinoids are synthesized postsynaptically but activate presynaptic cannabinoid receptor 1 (CB1) receptors to inhibit neurotransmitter release. In turn, CB1-expressing inhibitory and excitatory synapses act as strategically placed control points for activity-dependent regulation of dynamically changing normal and pathological oscillatory network activity. Here, we highlight emerging principles of cannabinoid circuit control and plasticity, and discuss their relevance for epilepsy and related comorbidities. New insights into cannabinoid signalling may facilitate the translation of the recent interest in cannabis-related substances as antiseizure medications to evidence-based treatment strategies.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Alger
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
authors.affiliation: Department of Impairment Study, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ohno-Shosaku
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D058256:Brain Waves; D063388:Endocannabinoids / Q000096:biosynthesis*; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D009415:Nerve Net / Q000503:physiopathology*; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1