In medium spiny neurons of the dorsal striatum, excitatory afferents from the cortex and dopamine fiber arising from the substantia nigra converge. If Gp1 mGluRs and D2Rs are activated concomitantly endocannabinoids. most likely anandamide, are synthesized and released from the MSN. This retrograde messenger activates presynaptic CB1 receptors, and reduced release probability via inhibition of calcium channels, cAMP and PKA, such that Rab3a and Rim1a dependent exocytosis is reduced. In Parkinson’s disease dopamine afferents are absent, and mGluR-LTD as a consequence reduced. This leads to increased indirect pathway activity (i.e. more inhibitory output from the GABAergic MSNs) and a reduction of spontaneous movements.