title: Aquaporin-4 deficiency facilitates fear memory extinction in the hippocampus through excessive activation of extrasynaptic GluN2B-containing NMDA receptors.
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'.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jie-Ting
authors.initials: JT
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, 430030, China; Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China; The Collaborative Innovation Center for Brain Science, Wuhan, 430030, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan, 430030, China; Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology, Wuhan, 430030, China; The Collaborative Innovation Center for Brain Science, Wuhan, 430030, China. Electronic address: wangfangtj0322@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D036881:Long-Term Synaptic Depression; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: C496032:Aqp4 protein, rat; D051401:Aquaporin 4; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
keywords: AQP-4; Fear memory extinction; Hippocampus; Long-term depression; NMDA receptor