title: Reward memory relieves anxiety-related behavior through synaptic strengthening and protein kinase C in dentate gyrus.
abstract: Anxiety disorders are presumably associated with negative memory. Psychological therapies are widely used to treat this mental deficit in human beings based on the view that positive memory competes with negative memory and relieves anxiety status. Cellular and molecular processes underlying psychological therapies remain elusive. Therefore, we have investigated its mechanisms based on a mouse model in which food reward at one open-arm of the elevated plus-maze was used for training mice to form reward memory and challenge the open arms. Mice with the reward training showed increased entries and stay time in reward open-arm versus neutral open-arm as well as in open-arms versus closed-arms. Accompanying with reward memory formation and anxiety relief, glutamatergic synaptic transmission in dentate gyrus in vivo and dendritic spines in granule cells became upregulated. This synaptic up-regulation was accompanied by the expression of more protein kinase C (PKC) in the dendritic spines. The inhibition of PKC by chelerythrine impaired the formation of reward memory, the relief of anxiety-related behavior and the up-regulation of glutamate synapses. Our results suggest that reward-induced positive memory relieves mouse anxiety-related behavior by strengthening synaptic efficacy and PKC in the hippocampus, which imply the underlying cellular and molecular processes involved in the beneficial effects of psychological therapies treating anxiety disorders.
authors.affiliation: State Key Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.|Qingdao University, Medical College, 38, Dengzhou, Shandong, China.
authors.forename: Zhuofan
authors.initials: Z
authors.lastname: Lei
authors.affiliation: State Key Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: State Key Laboratory, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.|University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000201:enzymology / Q000473:pathology / Q000523:psychology / Q000628:therapy*; D053119:Benzophenanthridines / Q000494:pharmacology; D049229:Dendritic Spines / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008811:Mice, Inbred DBA; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012201:Reward; D013569:Synapses / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D053119:Benzophenanthridines; D047428:Protein Kinase Inhibitors; D018698:Glutamic Acid; C016299:chelerythrine; D011493:Protein Kinase C
keywords: anxiety; hippocampus; memory; protein kinase C; synaptic plasticity