title: ASIC1a regulates insular long-term depression and is required for the extinction of conditioned taste aversion.
abstract: Acid-sensing ion channel 1a (ASIC1a) has been shown to play important roles in synaptic plasticity, learning and memory. Here we identify a crucial role for ASIC1a in long-term depression (LTD) at mouse insular synapses. Genetic ablation and pharmacological inhibition of ASIC1a reduced the induction probability of LTD without affecting that of long-term potentiation in the insular cortex. The disruption of ASIC1a also attenuated the extinction of established taste aversion memory without altering the initial associative taste learning or its long-term retention. Extinction of taste aversive memory led to the reduced insular synaptic efficacy, which precluded further LTD induction. The impaired LTD and extinction learning in ASIC1a null mice were restored by virus-mediated expression of wild-type ASIC1a, but not its ion-impermeable mutant, in the insular cortices. Our data demonstrate the involvement of an ASIC1a-mediated insular synaptic depression mechanism in extinction learning, which raises the possibility of targeting ASIC1a to manage adaptive behaviours.
authors.affiliation: Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, and Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Wei-Guang
authors.initials: WG
authors.lastname: Li
authors.affiliation: Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, and Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ming-Gang
authors.initials: MG
authors.lastname: Liu
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Shining
authors.initials: S
authors.lastname: Deng
authors.affiliation: Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, and Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Liu
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.affiliation: Institute of Neuroscience, National Yang-Ming University, 155, Section 2, Li-Nong Street, Taipei 112, Taiwan.
authors.forename: Tsan-Ting
authors.initials: TT
authors.lastname: Hsu
authors.affiliation: Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, and Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, and Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.|Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Developmental and Behavioral Pediatrics, Shanghai Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200129, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Michael Xi
authors.initials: MX
authors.lastname: Zhu
authors.affiliation: Discipline of Neuroscience, Department of Anatomy, Histology and Embryology, and Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Tian-Le
authors.initials: TL
authors.lastname: Xu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000172:deficiency / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003214:Conditioning, Classical / Q000187:drug effects; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry; D012118:Resorcinols / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013649:Taste / Q000187:drug effects / Q000502:physiology*
chemical_list: C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D005971:Glutamates; D010455:Peptides; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D000071679:Glycogen Synthase Kinase 3 beta; D005998:Glycine