Indeed, our finding that DHPG induces both synaptic and intrinsic forms of plasticity with greater efficacy in VH slices is consistent with this hypothesis, since increases in receptor density have been shown to lead to higher agonist efficacies in recombinant expression systems (Gazi et al., 1999; Hermans et al., 1999), and increased expression of mGlu5 has previously been associated with an enhanced level of DHPG-LTD in a rat model of treatment-resistant depression (Pignatelli et al., 2013). This evidence concerns the gene GRM5 and major depressive disorder.