Wang Shi, Pan De-Xi, Wang Dan, Wan Peng, Qiu De-Lai, Jin Qing-Hua
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.
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.
Behav Brain Res. 2014 Sep 1;271:177-83. doi: 10.1016/j.bbr.2014.06.011. Epub 2014 Jun 13.
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.
海马体是哺乳动物学习和记忆的关键结构，而长时程增强（LTP）是一种负责学习和记忆的重要细胞机制。尽管许多研究表明一氧化氮（NO）作为逆行信使参与LTP的形成和维持，但很少有研究将神经递质释放作为清醒动物的视觉指标来探究NO在依赖学习的突触效率长期增强中的作用。因此，在本研究中，在自由活动的清醒大鼠主动回避行为的习得和消退过程中，测量了海马齿状回（DG）区域中L-NMMA（一种NO合酶抑制剂）和SNP（一种NO供体）对细胞外谷氨酸（Glu）浓度和场兴奋性突触后电位（fEPSP）幅度的影响。在对照组中，DG中Glu的细胞外浓度在主动回避行为习得期间显著增加，并在消退训练后逐渐恢复到基线水平。在实验组中，局部微量注射L-NMMA显著降低了Glu浓度的变化，主动回避行为的习得也受到了抑制。相反，SNP显著增强了Glu浓度的变化，主动回避行为的习得显著加速。此外，在所有组中，细胞外Glu的变化伴随着fEPSP幅度和主动回避行为的相应变化。我们的结果表明，海马DG中的NO通过提高大鼠的谷氨酸水平和突触效率促进主动回避学习。
