title: Despair-associated memory requires a slow-onset CA1 long-term potentiation with unique underlying mechanisms.
abstract: The emotion of despair that occurs with uncontrollable stressful event is probably retained by memory, termed despair-associated memory, although little is known about the underlying mechanisms. Here, we report that forced swimming (FS) with no hope to escape, but not hopefully escapable swimming (ES), enhances hippocampal α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-dependent GluA1 Ser831 phosphorylation (S831-P), induces a slow-onset CA1 long-term potentiation (LTP) in freely moving rats and leads to increased test immobility 24-h later. Before FS application of the antagonists to block S831-P or N-methyl-D-aspartic acid receptor (NMDAR) or glucocorticoid receptor (GR) disrupts LTP and reduces test immobility, to levels similar to those of the ES group. Because these mechanisms are specifically linked with the hopeless of escape from FS, we suggest that despair-associated memory occurs with an endogenous CA1 LTP that is intriguingly mediated by a unique combination of rapid S831-P with NMDAR and GR activation to shape subsequent behavioral despair.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Jing
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Duan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Tian
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Tan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Yong-Yong
authors.initials: YY
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|School of Life Sciences, Anhui University, Hefei 230601, China.
authors.forename: Ze-Yang
authors.initials: ZY
authors.lastname: Ding
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yue-Xiong
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Institute of Mental Health Research and Departments of Psychiatry and Cellular &Molecular Medicine, University of Ottawa, 1145 Carling Ave, Ottawa, Ontario, K1Z 7K4, Canada.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Mao
authors.affiliation: Sagol Department of Neurobiology and Department of Psychology, University of Haifa, Haifa, Israel.|The Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Richter-Levin
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming 650223, China.|University of the Chinese Academy of Sciences, Beijing 100049, China.|CAS Center for Excellence in Brain Science, 320 Yue Yang Road, Shanghai, 200031, China.|Mental Health Institute, the Second Xiangya Hospital of Central South University, Changsha 410011, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D003863:Depression / Q000503:physiopathology / Q000523:psychology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D015151:Immunoblotting; D007649:Ketamine / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology; D013550:Swimming / Q000502:physiology / Q000523:psychology
chemical_list: D003345:Corticosterone; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D000451:Mineralocorticoid Receptor Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D011965:Receptors, Glucocorticoid; D016194:Receptors, N-Methyl-D-Aspartate; D013148:Spironolactone; C498554:5-(alpha-methyl-4-bromobenzylamino)phosphonomethyl-1,4-dihydroquinoxaline-2,3-dione