title: Neuron to astrocyte communication via cannabinoid receptors is necessary for sustained epileptiform activity in rat hippocampus.
abstract: Astrocytes are integral functional components of synapses, regulating transmission and plasticity. They have also been implicated in the pathogenesis of epilepsy, although their precise roles have not been comprehensively characterized. Astrocytes integrate activity from neighboring synapses by responding to neuronally released neurotransmitters such as glutamate and ATP. Strong activation of astrocytes mediated by these neurotransmitters can promote seizure-like activity by initiating a positive feedback loop that induces excessive neuronal discharge. Recent work has demonstrated that astrocytes express cannabinoid 1 (CB1) receptors, which are sensitive to endocannabinoids released by nearby pyramidal cells. In this study, we tested whether this mechanism also contributes to epileptiform activity. In a model of 4-aminopyridine induced epileptic-like activity in hippocampal slice cultures, we show that pharmacological blockade of astrocyte CB1 receptors did not modify the initiation, but significantly reduced the maintenance of epileptiform discharge. When communication in astrocytic networks was disrupted by chelating astrocytic calcium, this CB1 receptor-mediated modulation of epileptiform activity was no longer observed. Thus, endocannabinoid signaling from neurons to astrocytes represents an additional significant factor in the maintenance of epileptiform activity in the hippocampus.
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: Guyllaume
authors.initials: G
authors.lastname: Coiret
authors.forename: Jeanne
authors.initials: J
authors.lastname: Ster
authors.forename: Benjamin
authors.initials: B
authors.lastname: Grewe
authors.forename: Fabrice
authors.initials: F
authors.lastname: Wendling
authors.forename: Fritjof
authors.initials: F
authors.lastname: Helmchen
authors.forename: Urs
authors.initials: U
authors.lastname: Gerber
authors.forename: Pascal
authors.initials: P
authors.lastname: Benquet
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1; D015761:4-Aminopyridine