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We found that coactivation of<jats:italic>N<\/jats:italic>-methyl-<jats:sc>d<\/jats:sc>-aspartate receptors (NMDAR) and type 1 cannabinoid receptors (CB1R) induces long-term depression (LTD) at the synapse between the central shell and the external portion of the inferior colliculus of the chicken. Although endocannabinoids are commonly thought of as presynaptic modulators, recent reports have suggested that they can also modulate the postsynaptic site. In the avian midbrain, we found that LTD is mediated by both presynaptic and postsynaptic changes. The presynaptic mechanism consists of a decrease in neurotransmitter release, whereas a depression of NMDAR-mediated current takes place on the postsynaptic side. Both the presynaptic and the postsynaptic effects depend on CB1R activation. 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