Neuron. 2007 Jun 7;54(5):801-12.

Endocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and RIM1alpha.

Chevaleyre V, Heifets BD, Kaeser PS, Südhof TC, Castillo PE.

Source

Dominick P. Purpura [corrected] Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Erratum in

Neuron. 2007 Jul 5;55(1):169. Purpura, Dominick P [removed].

Abstract

Endocannabinoids (eCBs) have emerged as key activity-dependent signals that, by activating presynaptic cannabinoid receptors (i.e., CB1) coupled to G(i/o) protein, can mediate short-term and long-term synaptic depression (LTD). While the presynaptic mechanisms underlying eCB-dependent short-term depression have been identified, the molecular events linking CB1 receptors to LTD are unknown. Here we show in the hippocampus that long-term, but not short-term, eCB-dependent depression of inhibitory transmission requires presynaptic cAMP/PKA signaling. We further identify the active zone protein RIM1alpha as a key mediator of both CB1 receptor effects on the release machinery and eCB-dependent LTD in the hippocampus. Moreover, we show that eCB-dependent LTD in the amygdala and hippocampus shares major mechanistic features. These findings reveal the signaling pathway by which CB1 receptors mediate long-term effects of eCBs in two crucial brain structures. Furthermore, our results highlight a conserved mechanism of presynaptic plasticity in the brain.