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

  • Can J Psychiatry. 2020 May;65(5):347-355. doi: 10.1177/0706743719874162.
Xiangzhi Jiang  1 ,  Wei Lin  2 ,  Yuanyuan Cheng  3 ,  Dongming Wang  4
Affiliations
  • 1. Psychiatric Outpatient, Qingdao Mental Health Center, Qingdao, China.
  • 2. Open Mental Department, Qingdao Mental Health Center, Qingdao, China.
  • 3. Psychosis Department Ⅰ, Qingdao Mental Health Center, Qingdao, China.
  • 4. Old Age Psychosis Department Ⅱ, Qingdao Mental Health Center, Qingdao, China.
PMID: 31526043 DOI: 10.1177/0706743719874162
Abstract

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.

Keywords
CSDS; MDD; NMDAR; mGluR5; synaptic strength.
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