期刊
NEUROPHARMACOLOGY
卷 112, 期 -, 页码 124-134出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.06.031
关键词
AQP-4; Hippocampus; NMDA receptor; Fear memory extinction; Long-term depression
资金
- National Basic Research Program of China [2013CB531303, 2014CB744601]
- National Natural Scientific Foundation of China [81471377]
- National Key Scientific Instrument and Equipment Development Project of China [2013YQ03092306]
- PCSIRT [IRT13016]
- Science Fund for Creative Research Groups of the Natural Science Foundation of Hubei Province [2015CFA020]
Aquaporin-4 (AQP-4) is the predominant water channel in the brain and primarily expressed in astrocytes. Astrocytes have been generally believed to play important roles in regulating synaptic plasticity and information processing. A growing number of evidence shows that AQP-4 plays a potential role in the regulation of astrocyte function. However, little is known about the function of AQP-4 for synaptic plasticity in the hippocampus. Therefore, we evaluated long-term depression (LTD) in the hippocampus and the extinction of fear memory of AQP-4 knockout (KO) and wild-type (WT) mice. We found that AQP-4 deficiency facilitated fear memory extinction and NMDA receptors (NMDARs)-dependent LTD in the CA3-CA1 pathway. Furthermore, AQP-4 deficiency selectively increased GluN2B-NMDAR-mediated excitatory postsynaptic currents (EPSCs). The excessive activation of extrasynaptic GluN2B-NMDAR contributed to the facilitation of NMDAR-dependent LTD and enhancement of fear memory extinction in AQP-4 KO mice. Thus, it appears that AQP-4 may be a potential target for intervention in fear memory extinction. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'. (C) 2016 Elsevier Ltd. All rights reserved.
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