Effects Of No On The Learning-dependent Ltp In Hippocampal Dg Region In Conscions Rats

Hippocampus is one of the key structure for learning and memory in mammals, and long-term potentiation (LTP) is an important mechanism responsible for the learning and memory in the hippocampus. Recent evidences have shown that both presynaptic and postsynaptic mechanisms are involved in the formation and maintenance of LTP, especially the maintenance of LTP is associated with high level release of neurotransmitter from presynaptic membrane induced by retrograde messengers which synthesize and release from postsynaptic neurons. Although a number of studies indicate that nitric oxide (NO) involved in the formation and maintenance of LTP as a retrograde messenger, but the majority of these studies were in vitro experiments, even if the in vivo experiments only observed the formation of LTP when the NO was changed by NO donor or NOS inhibitor and rarely considered using a neurotransmitter release as a visual indicator in awake animal to explore the effects of NO. Therefore, in order to investigate the effects of NO in the learning-dependent LTP in hippocampal DG reigon, SNP, a NO donor, is locally microinjected into the hippocampal dentate gyrus (DG) region, then the extracellular concentration of amno acids in DG region is measured during the period of establishment and experimental extinction of the conditioned reflex in free-moving conscious rats as well as amplitude of population spike (PS, a detection parameter of LTP).Results:1, The extracellular levels of Asp, Glu, Gly and Ala in the DG region are signifi-cantly increased (P<0.01, P<0.001, P<0.001, P<0.01, respectively) by local-microinjection of SNP (10μg/ml) and the PS amplitude in the DG region is also increased (P<0.001) by SNP without training. The upward trend of PS was roughly same as the amino acids. 2, In the control group2, the extracellular levels of Glu and Gly in the DG region are significantly increased (P<0.05, P<0.01, P<0.05, respectively) during the establishment of conditioned reflex and gradually returned following the extinction of conditioned reflex. The changes of amino acids are correlated to the change of PS and both changes roughly follow the correct rate of behavior.3, In experimental group2, the changes of concentration of Asp, Glu, Gly and PS are significantly enhanced by local-microinjection of SNP, as well as the establishment of conditioned reflex is significantly accelerated and the extinction is significantly delayed by SNP.4, In DG region microinjection of SNP significantly accelerated the formation of conditioned reflex and delayed the extinction of conditioned reflex, concentrations of Asp, Glu, Gly and PS amplitude in the formation of conditioned reflex were significantly higher than the control group.Conclusion:NO is involved in the formation and maintenance of learning-dependent LTP, which may be via enhancing the presynaptic release of Asp, Glu and Gly in hippocampal DG region.