| First Author | Shi MM | Year | 2020 |
| Journal | Mol Psychiatry | Volume | 25 |
| Issue | 5 | Pages | 977-992 |
| PubMed ID | 31142818 | Mgi Jnum | J:342785 |
| Mgi Id | MGI:6714592 | Doi | 10.1038/s41380-019-0435-z |
| Citation | Shi MM, et al. (2020) Hippocampal micro-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval. Mol Psychiatry 25(5):977-992 |
| abstractText | Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the micro-opioid receptor (muR), one of the major opioid receptors, strongly influences memory processing in that alterations in muR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether muR signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective muR depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal muR signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal muRs were significantly activated during acute stress. Blockage of hippocampal muRs, non-selective deletion of muRs or selective deletion of muRs on GABAergic neurons (muRGABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a muRGABA-dependent manner. Pharmaceutically enhancing hippocampal GABAA receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate muRGABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval. |
