Nondeclarative Taste Memory And Negative Emotion Behaviors In NR2B Transgenic Mice

N-methyl-D-aspartic(NMDA) receptor is one of the essential excitability glutamate ionotropic receptors,and one of its key functional subunit is NR2B subunit. Over-expression of NR2B subunit prolongs the activation of NMDA receptors,and forebrain NR2B transgenic mice exhibite significant advantage in a series of behavior tasks which related to declarative memory;however,further study focuse on effect of NR2B subunit in nondeclarative learning and memory ability is still needed.Using various molecular and behavior analysis in forebrain NR2B transgenic mice(Tg mice), we studied the effects of forebrain over-expressed NMDA receptor 2B subunit on multiple conditioned taste aversion tasks,in order to reveal the role of NR2B subunit in nondeclarative learning and memory.Besides,former researches indicated that the NR2B subunit may involved in the pathogenesis of negative emotion disorders like anxiety and schizophrenia,which may influence the learning and memory procedures.Therefore we next compared the anxiety-like and schizophrenia-like behavior between both Tg and Wt mice,and usd capillary electrophoresis to analyse the monoamine neurotransmitter level in subregions of mice forebrain.These results suggest that the increased NR2B subunit expression enhanced the establishment of conditioned taste aversion,and had no effect on negative emotion of Tg mice.1.Mice production,genotype analysis and the expression of NR2B receptorThe SV40 primers were designed to detect the exogenous gene of NR2B subunit from genomic DNA isolated from terminal of mice tails for genotype analysis.Real Time PCR(RT-PCR) strategy was applied to identify the expression of NR2B gene in hypothalamus.Both the analyses and former research on same NR2B Tg mice of others showed that the NR2B gene was over-expressed in Tg mice.2.Nondeclarative taste memory of NR2B transgenic miceIn this study,we found that Tg mice showed significantly enhanced CTA 2 days after training,and CTA decreased more steadily than that of Wt mice in the fast extinction.On the 30th day after training,both Tg and Wt mice shared the same level of aversive memory,but in long term extinction experiments tested on the 60th,120th and 210th day,Tg mice maintained a better aversive memory than the controls.In addition,no difference between the two groups of mice was found in basic latent inhibition(LI) and two-taste LI experiment.These data suggested that forebrain NR2B over-expression had different effects on learning and memory of gustation:enhanced the quick acquisition of CTA,and had no significant influence on long term CTA, familiar taste recognition and extinction of CTA.3.Anixty-like behavior of NR2B transgenic miceIn our experiments,the results indicated that the juvenile,middle-aged and old Tg mice showed no significant difference in open field test and elevated plus maze test as compared with Wt mice.These results suggest that the forebrain increase of NR2B subunit had no significant effect on anxiety-related behaviors in mice.4.Schizophrenia-like behavior of NR2B transgenic miceIn this study,NR2B Tg mice showed normal inhibition ratio in prepulse inhibition task and latent inhibition task,as its control littermates.The results indicate that the increased expression level of forebrain NR2B subunit will not augment the risk of schizophrenia. 5.Monoamine neurotransmitter level in subregions of mice forebrainThe results of capillary electrophoresis showed monoamine neurotransmitter level in subregions of Tg mice forebrain revealed no significant difference between Tg and Wt mice.