Figure 7.

Model of CB1R modulation of neuronal morphology and AIS. Schematic showing the functional implication of CB1R activity at different stages of neuronal development in vitro. Neuronal developmental stages 1–5 have been defined previously by Dotti et al. (1988). Stage 3 is characterized by axonal polarization and elongation, while dendritogenesis and AIS development occurs from stages 4–5. In both cases, figures represent the effect of CB1R inhibition or suppression at stage 1, when neurons are not yet polarized. Left, during initial stages of neuronal polarization and axonal elongation, CB1Rs display low or negligible activity (red) in the axon. Exogenous or endogenous increase of 2-AG level (through MAGL inhibition, red dots; or exogenous application, green dots) promotes axonal elongation and branching through CB1R activation (blue). Evidence so far suggests that endogenous 2-AG may come from glial or neuronal cells. Right, at later stages of neuronal development (stages 4–5), CB1R activity (blue) in the dendrites and/or in the axons terminals and synapses contributes to dendritic and AIS development. Reducing CB1R activity or expression (red) impedes dendritic growth and reduces ankyrinG levels in the AIS.