Figure 8

Expression of mRNA for endocannabinoid receptor and metabolic enzymes across development. qPCR data in our tissue cohort are represented schematically in the context of an inhibitory DLPFC synapse. Note that the size of each coloured mRNA reflects the relative magnitude of expression at different developmental points, not absolute mRNA levels. Arrow thickness represents relative prominence of signalling or enzymatic breakdown at each point. A Early life (neonate to toddler age) is characterised by robust potential for endocannabinoid modification of presynaptic neurotransmission (suggested by moderate 2-AG synthesis, low levels of postsynaptic 2-AG hydrolysis, high CB₁R mRNA and low anandamide synthesis). B Adolescence is represented by increased potential for endocannabinoid modification of presynaptic input (suggested by elevated 2-AG synthesis), but reduced potency of such endocannabinoid modification compared with early life (reflected by reduced CB₁R mRNA and increased anandamide synthesis). C By adulthood, modification of presynaptic neurotransmission by endocannabinoids may be minimal: despite reduced presynaptic 2-AG hydrolysis, there may be reduced capacity for retrograde 2-AG signalling due to reduced postsynaptic 2-AG synthesis and increased postsynaptic 2-AG hydrolysis, and CB₁R mRNA is reduced. Anandamide turnover peaks at adulthood, suggesting increased prominence in signalling at CB₁R or other receptors such as TRPV1.