“…In cultured hippocampal neurons, CB1R has a wide intracellular distribution but its plasma membrane surface expression is highly polarized toward the axonal compartment (Figure 1; Irving et al, 2000;Coutts et al, 2001;Leterrier et al, 2006;McDonald et al, 2007a;Fletcher-Jones et al, 2019). CB1R displays a disto-proximal gradient of CB1R expression along the entire axonal plasma membrane (Simon et al, 2013;Wickert et al, 2018) with fine axons reported to exhibit highly punctate surface labeling, often co-localized with sites of synaptic contact (Irving et al, 2000;Coutts et al, 2001). Immunogold electron microscopy analysis of rat brain sections (Katona et al, 1999;Nyiri et al, 2005) and STORM super-resolution imaging (Dudok et al, 2015) detect CB1R predominantly at the presynaptic terminal, concentrated in the plasma membrane at axonal perisynaptic regions of both GABAergic and glutamatergic neurons (Katona et al, 1999(Katona et al, , 2006Kawamura et al, 2006).…”