| First Author | Zhang B | Year | 2017 |
| Journal | Neuropharmacology | Volume | 116 |
| Pages | 387-398 | PubMed ID | 28108357 |
| Mgi Jnum | J:272139 | Mgi Id | MGI:6282678 |
| Doi | 10.1016/j.neuropharm.2017.01.014 | Citation | Zhang B, et al. (2017) Sigma-1 receptor deficiency reduces GABAergic inhibition in the basolateral amygdala leading to LTD impairment and depressive-like behaviors. Neuropharmacology 116:387-398 |
| abstractText | Sigma-1 receptor knockout (sigma1R(-/-)) in male mice causes depressive-like phenotype. We observed the expression of sigma1R in principal neurons of basolateral amygdala (BLA), a main region for affective regulation. The present study investigated the influence of sigma1R deficiency in BLA neurons on synaptic properties and plasticity at cortico-BLA pathway. In comparison with wild-type (WT) mice, the slopes of field excitatory postsynaptic potentials (fEPSP) were reduced in sigma1R(-/-) mice with the increases in paired-pulse facilitation (PPF) and paired-pulse inhibition (PPI) values. Induction of NMDA receptor (NMDAr)-dependent long-term potentiation (LTP) and NMDAr-independent long-term depression (LTD) were impaired in sigma1R(-/-) mice. The NMDAr NR2B phosphorylation in BLA of sigma1R(-/-) mice was lower than in WT mice. The coupling of nNOS to PSD-95 and nitric oxide (NO) level were reduced in BLA of sigma1R(-/-) mice, which were recovered by the BLA-injection of NMDAr agonist NMDA. The bath-application of NMDA in BLA slices from sigma1R(-/-) mice corrected the reduced fEPSP slopes and increased PPF and PPI and recovered the LTP and LTD induction, which were sensitive to nNOS inhibitor 7-NI. NO donor DETA/NO or GABAAR agonist muscimol could correct the PPI and recover LTD in sigma1R(-/-) mice. In addition, the BLA-injection of NMDA, DETA/NO or muscimol could relieve the depressive-like behaviors in sigma1R(-/-) mice. These results indicate that the sigma1R deficiency in BLA principal neurons via NMDAr dysfunction suppresses nNOS activity and NO production to reduce GABAAR-mediated inhibition, which impairs LTD induction and causes depressive-like phenotype. |
