title: Nitric oxide facilitates active avoidance learning via enhancement of glutamate levels in the hippocampal dentate gyrus.
abstract: The hippocampus is a key structure for learning and memory in mammals, and long-term potentiation (LTP) is an important cellular mechanism responsible for learning and memory. Despite a number of studies indicating that nitric oxide (NO) is involved in the formation and maintenance of LTP as a retrograde messenger, few studies have used neurotransmitter release as a visual indicator in awake animals to explore the role of NO in learning-dependent long-term enhancement of synaptic efficiency. Therefore, in the present study, the effects of l-NMMA (a NO synthase inhibitor) and SNP (a NO donor) on extracellular glutamate (Glu) concentrations and amplitudes of field excitatory postsynaptic potential (fEPSP) were measured in the hippocampal dentate gyrus (DG) region during the acquisition and extinction of active-avoidance behavior in freely-moving conscious rats. In the control group, the extracellular concentration of Glu in the DG was significantly increased during the acquisition of active-avoidance behavior and gradually returned to baseline levels following extinction training. In the experimental group, the change in Glu concentration was significantly reduced by local microinjection of l-NMMA, as was the acquisition of the active-avoidance behavior. In contrast, the change in Glu concentration was significantly enhanced by SNP, and the acquisition of the active-avoidance behavior was significantly accelerated. Furthermore, in all groups, the changes in extracellular Glu were accompanied by corresponding changes in fEPSP amplitude and active-avoidance behavior. Our results suggest that NO in the hippocampal DG facilitates active avoidance learning via enhancements of glutamate levels and synaptic efficiency in rats.
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, 977 Gongyuan Road, Yanji 133002, Jilin Province, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, 977 Gongyuan Road, Yanji 133002, Jilin Province, China; China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, Jilin Province, China.
authors.forename: De-Xi
authors.initials: DX
authors.lastname: Pan
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, 977 Gongyuan Road, Yanji 133002, Jilin Province, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, 977 Gongyuan Road, Yanji 133002, Jilin Province, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wan
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, 977 Gongyuan Road, Yanji 133002, Jilin Province, China.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
authors.affiliation: Department of Physiology and Pathophysiology, Yanbian University College of Medicine and Cellular Function Research Center, Yanbian University, 977 Gongyuan Road, Yanji 133002, Jilin Province, China. Electronic address: yqinghua@ybu.edu.cn.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Jin
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D018891:Dentate Gyrus / Q000378:metabolism* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D018698:Glutamic Acid / Q000032:analysis*; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008845:Microinjections; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D018794:Problem-Based Learning; D051381:Rats; D017208:Rats, Wistar; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D018698:Glutamic Acid
keywords: Active avoidance learning; Glutamate level; Hippocampal dentate gyrus; Nitric oxide; Synaptic efficiency