Figure 2.

An abbreviated model for endocannabinoid synthesis and release during LTD in the striatum and NAc. In both areas, LTD is expressed presynaptically, due to the activity-dependent release of endocannabinoids as retrograde messengers. Activation of group I mGluRs is necessary for this plasticity, probably as a means for elevating postsynaptic Ca²⁺ (L-type voltage-gated Ca²⁺ channels are also involved in dorsal striatum). Ca²⁺-dependent pathways of AEA synthesis are shown with red arrows. D2 dopamine receptors are also necessary for LTD in the dorsal striatum, where D2 receptors stimulate formation of AEA, especially in conjunction with depolarizing stimuli. Note that the activation of PLC by mGluRs may also lead to the formation of 2-AG through a Ca²⁺-independent DAG lipase activity. The efflux of AEA or 2-AG from striatal neurons may involve an AMT, although this is controversial. Symbols and abbreviations: AMPAR, AMPA subtype glutamate receptor; DAG, diacylglycerol; IP₃, inositol trisphosphate; NAPE, n-acylphosphatidylethanolamine; PLD, NAPE-specific phospholipase D; ΔΨ, depolarization; •, glutamate.