title: Aquaporin-4 deficiency impairs synaptic plasticity and associative fear memory in the lateral amygdala: involvement of downregulation of glutamate transporter-1 expression.
abstract: Astrocytes are implicated in information processing, signal transmission, and regulation of synaptic plasticity. Aquaporin-4 (AQP4) is the major water channel in adult brain and is primarily expressed in astrocytes. A growing body of evidence indicates that AQP4 is a potential molecular target for the regulation of astrocytic function. However, little is known about the role of AQP4 in synaptic plasticity in the amygdala. Therefore, we evaluated long-term potentiation (LTP) in the lateral amygdala (LA) and associative fear memory of AQP4 knockout (KO) and wild-type mice. We found that AQP4 deficiency impaired LTP in the thalamo-LA pathway and associative fear memory. Furthermore, AQP4 deficiency significantly downregulated glutamate transporter-1 (GLT-1) expression and selectively increased NMDA receptor (NMDAR)-mediated EPSCs in the LA. However, low concentration of NMDAR antagonist reversed the impairment of LTP in KO mice. Upregulating GLT-1 expression by chronic treatment with ceftriaxone also reversed the impairment of LTP and fear memory in KO mice. These findings imply a role for AQP4 in synaptic plasticity and associative fear memory in the amygdala by regulating GLT-1 expression.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, China.
authors.forename: Yan-Kun
authors.initials: YK
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Xiao
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Hu
authors.forename: You
authors.initials: Y
authors.lastname: Jin
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
mesh_terms: D000679:Amygdala / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D002443:Ceftriaxone / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005239:Fear / Q000523:psychology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013788:Thalamus / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051401:Aquaporin 4; D027342:Excitatory Amino Acid Transporter 2; D016194:Receptors, N-Methyl-D-Aspartate; D002443:Ceftriaxone