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- supplemental material - Supplemental Figure 1. Model of eCB-LTD at excitatory synapses onto medium spiny neurons Activation of postsynaptic mGluR1/5, along with coincident subthreshold depolarization of medium spiny neurons sufficient to activate L-type voltage-sensitive calcium channels (VSCCs), stimulates the postsynaptic synthesis and release of endocannabinoids, perhaps via PLCβ (Hashimotodani et al., 2005). Co-activation of postsynaptic dopamine D2-type receptors (D2R) enhances endocannabinoid production and the subsequent induction of presynaptic LTD, mediated through activation of presynaptic CB1 receptors (CB1R).