Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens

Abstract

Actions Concertées Incitatives "Jeunes Chercheurs" Plasticité Synaptique et Toxicomanie, Centre National de la Recherche Scientifique, Unité Propre de Recherche 9023, 141 Rue de la Cardonille, 34094 Montpellier Cedex 05, France Do endocannabinoids (eCBs) participate in long-term synaptic plasticity in the brain? Using pharmacological approaches and genetically altered mice, we show that stimulation of prelimbic cortex afferents at naturally occurring frequencies causes a long-term depression of nucleus accumbens glutamatergic synapses mediated by eCB release and presynaptic CB1 receptors. Translation of glutamate synaptic transmission into eCB retrograde signaling involved metabotropic glutamate receptors and postsynaptic intracellular Ca2+ stores. These findings unveil the role of the eCB system in activity-dependent long-term synaptic plasticity and identify a mechanism by which marijuana can alter synaptic functions in the endogenous brain reward system.