mGluR5 Facilitates Long-Term Synaptic Depression in a Stress-Induced Depressive Mouse Model

Background: Glutamatergic system has been known to play a role in the pathogenesis of major depression disorder by inducing N-methyl-d-aspartate receptor-dependent long-term depression (LTD) or Metabotropic Glutamate Receptors (mGluR)-dependent LTD. Here, we characterized the LTD in a chronic social defeat stress (CSDS)-induced depressive mouse model.

Methods: CSDS was used to induce the depressive-like behaviors in C57BL/6 male mice, which were assessed using sucrose preference test and social interaction test. The synaptic strength including LTD and long-term potentiation (LTP) induced by paired-pulse low frequency stimulation (PP-LFS) was measured using whole-cell recording technique.

Results: CSDS induced depressive-like behaviors and facilitated PP-LFS-induced LTD in hippocampal CA3-CA1 pathway in the susceptible mice. Interestingly, mGluR5 but not N-methyl-d-aspartate receptor mediated the PP-LFS-induced LTD. In addition, mGluR5 Agonist dihydroxyphenylglycine promoted PP-LFS-induced LTD specifically in susceptible mice, which was diminished by activating the BDNF/TrkB signaling pathway.

Conclusions: Our results suggest that mGluR5-dependent LTD might be responsible for the development of depressive-like behaviors in CSDS-induced depression mice model.

CSDS; MDD; NMDAR; mGluR5; synaptic strength.