Aquaporin-4 deficiency facilitates fear memory extinction in the hippocampus through excessive activation of extrasynaptic GluN2B-containing NMDA receptors. (January 2017)

• Record Type: Journal Article
• Authors: Wu, Xin; Zhang, Jie-Ting; Li, Di; Zhou, Jun; Yang, Jun; Zheng, Hui-Ling; Chen, Jian-Guo; Wang, Fang
• Is Part Of: Neuropharmacology. Volume 112:Part A(2017)
• Page Start: 124
• Page End: 134
• Publication Date: 2017-01
• Subjects: AQP-4 -- Hippocampus -- NMDA receptor -- Fear memory extinction -- Long-term depression; ACSF artificial cerebrospinal fluid -- AQP-4 Aquaporin-4 -- CNQX 6-cyano-7-nitroquinoxaline-2, 3-dione -- CNS central nervous system -- DL-APV dl-amino-phosphonovaleric acid -- EPSCs excitatory postsynaptic currents -- ERK extracellular signal-regulated kinase -- fEPSPs field excitatory postsynaptic potentials -- GLT-1 glutamate transporter-1 -- IOR input-output relationship -- KO knockout -- LFS low-frequency stimulation -- LTD long-term depression -- LTP long-term potentiation -- MCPG (RS)-a-methyl-4-carboxyphenylglycine -- mGluR metabotropic glutamate receptor -- NMDA N-methyl-d-aspartate -- P38 MAPK P38 mitogen activated kinase -- PEAQX ({[(1S)-1-(4-bromophenyl)ethyl]amino}-(2, 3-dioxo-1, 4-dihydroquinoxalin-5-yl)methyl)phosphonic acid -- PPF paired-pulse facilitation -- TBS theta-burst stimulation -- TTX tetrodotoxin; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.06.031
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: 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'. Highlights: AQP-4 deficiency facilitates fear extinction. AQP-4 deficiency facilitates NMDAR-LTD in the CA3-CA1 pathway. Excessive activation of extrasynaptic GluN2B-NMDAR contributes to the changes in AQP-4 KO mice.