FIGURE 1.

Schematic of the synaptic organization of the ECS. (A) The ECS is highly polarized and unlike nearly all neurotransmitter systems it acts retrogradely. The most abundant endocannabinoid, 2-arachidonoylglycerol (2-AG), is synthesized by the postsynaptic enzyme DAGLα and released to activate presynaptically localized cannabinoid receptors (CB1R) to suppress neurotransmitter release and reduce synaptic activity. (B) Representative image of total and surface expression of N-terminally GFP-tagged CB1R. CB1R is widely distributed in intracellular compartments in neurons, but only stably surface expressed in axons, particularly at the axon terminal. The image shows surface (non-permeabilized, purple) and total (permeabilized, green; colocalization shows as white) CB1R labeled with anti-GFP antibody. The axon was identified by Ankyrin G labeling, red (triple colocalization shows as yellow) (Fletcher-Jones et al. previously unpublished image). (C) Correspondingly, DAGLα is highly localized at the postsynapse. GFP-DAGLα (human) expressed in hippocampal neurons is highly punctate in dendrites consistent with postsynaptic localization (blue = low intensity, purple = high intensity) (Fletcher-Jones et al. previously unpublished image).