Synaptic Plasticity And Emotional Memory Of Amygdala In NR2A Transgenic Mice

NMDA receptor is typically a heteromeric complex composed of different subunits and plays an important role in learning and memory. The NR2 subunits that are incorporated into NMDARs control the function of the receptors. Current research shows that the overexpression of NR2B subunit leads to the decrease in the NR2A/NR2B ratio and prolongs the activation of NMDARs, which elicits an increasing LTP. Behavioral tests show that the transgenic mice also have good performances in learning and memory. The question is what we will find if the NR2A subunit is upregulated?Using the molecular, electrophysiological and behavioral techniques, LTP, LTD and amygdala-related behaviors were studied in NR2A transgenic mice. Field potential recordings from amygdala slices show deficits in LTP corresponding with the decreased amygdala-dependent emotional memory. These results suggest that the increased ratio of NR2A/NR2B in amygdala would decrease the LTP in LA/BLA pathway and further impair the emotion-related learning and memory.1. Genotype analysis and the expression of NR2A receptorThe SV40 primers were designed to clone NR2A receptor gene from genomic DNA isolated from mice tails for genotype analysis. RT-PCR strategy was also applied to identify the expression of NR2A gene. Both analyses showed that the NR2A gene was overexpressed in cortex and amygdala in transgenic mice.2. Amygdala synaptic plasticity in NR2A transgenic miceUsing the field potential recording, we have studied the synaptic transmission and plasticity (LTP, LTD) in amygdala. Compared with the wild type littermates, the transgenic mice showed a deficit LTP, but were normal in basic synaptic transmission and LTD. With the NMDAR and NR2A antagonist administration, we demonstrated that NR2A subunit played a part in the LTP in amygdala. However, the final function of this gene may depend on the ratio of NR2A/NR2B.3. The basic and emotional behavior of NR2A transgenic miceSome basic behavioral tasks such as open field, pain sensitivity, elevated plus maze and forced swim test were used to study the basic activity and emotion in NR2A transgenic mice compared to the wild type littermates before further studies. All the tests showed no significant changes on the locomotor activity, exploration, emotion and innate fear between these two groups.4. The learning and memory behavior of NR2A transgenic micePassive avoidance and odor-reward associative learning tasks were performed to evaluate the learning and memory ability in transgenic mice. Mice were tested separately at the first and third day after the training. Transgenic mice in both delays showed an impaired learning and memory. But the performance in odor-reward test suggested that NR2A subunit may play an important role in memory consolidation and retrieval.