Presynaptic mGlu2 receptors gate glutamate release probability in PFC. At synapses arising from the MDT, presynaptic mGlu2 receptors can induce a long-term depression (LTD) of excitatory transmission. By contrast, neuronal mGlu3 receptors mediate a postsynaptic form of LTD. Postsynaptic mGlu3 LTD proceeds through the coordinated signaling of mGlu5 receptors, phosphoinositide 3-kinase (PI3K), Akt, glycogen synthase kinase-3 (GSK-3), and the internalization of AMPA receptors. mGlu3 LTD is also differentially expressed across long-range inputs to PFC, having been observed at synapses arising from the MDT and BLA, but not the ventral hippocampus.