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Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval.


ABSTRACT: 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 µ-opioid receptor (?R), one of the major opioid receptors, strongly influences memory processing in that alterations in ?R signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether ?R signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective ?R depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal ?R signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal ?Rs were significantly activated during acute stress. Blockage of hippocampal ?Rs, non-selective deletion of ?Rs or selective deletion of ?Rs on GABAergic neurons (?RGABA) 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 ?RGABA-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 ?RGABA 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.

SUBMITTER: Shi MM 

PROVIDER: S-EPMC7192851 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Hippocampal µ-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval.

Shi Mei-Mei MM   Fan Ka-Min KM   Qiao Yan-Ning YN   Xu Jin-Hui JH   Qiu Li-Juan LJ   Li Xiao X   Liu Ying Y   Qian Zhao-Qiang ZQ   Wei Chun-Ling CL   Han Jing J   Fan Juan J   Tian Ying-Fang YF   Ren Wei W   Liu Zhi-Qiang ZQ  

Molecular psychiatry 20190529 5


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 µ-opioid receptor (μR), one of the major opioid receptors, strongly influences memory processing in that alterations in μR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether μR signalling contributes to memory impairments induced by acute stress. Here  ...[more]

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