The Role Of NMDA Receptor Subunit 2B In The Development Of Auditory Function Of C57BI/6 Mice

Previous studies made in our lab indicated that monaural plugging during the critical period of postnatal development would reduce the special sensitivity of the auditory neurons in the contrary auditory cortex of the plugged ear, with the decrease of NMDA receptor density and its subunits expression in the relative cortex of the adult animal. This suggested that NMDA receptor must play a role in the plasticity of brain auditory functional development.In this study, we implanted a pipe on the surface of the left auditory cortex in C57B1/6 mice, during their critical period, then chronically administrated the NMDA receptor 2B subunit antagonist MK-801 though the pipe for 10 days. Using behavioral, electrophysiological and histological method, we studied the influence of chronically administrating of MK-801 during the critical period on the developmentivof auditory function development.1. The influence of NR2B on the behavior of auditory spatial discriminationUsing the food conditioned reflex, we compared the behavior of auditory spatial discrimination among the adult mice of control group, sham group and MK-801 group.The mice in MK-801 group needed more training to establish the food conditioned reflex and longer time (>65%) to complete a reflection, compared to the mice in control group and sham group. The deviation error of auditory spatial discrimination of the MK-801 group was much larger (>210%) than that of the other two groups.The result proved that the auditory spatial discrimination ability of the mice in MK-801 group was much poorer than that in control group and sham group.2. The influence of NR2B on the spatial sensitivity development of auditory cortex neuronsUsing the electrophysiological method, we investigated the spatial sensitivity of auditory cortex neurons of the adult mice in control group, sham group and MK-801 group.The distribution of auditory neurons of MK-801 group was limited in a smaller area of auditory cortex than the other two groups.There were few neurons detected in the area and near the area once implanted the pipe and administrated MK-801 in MK-801 group. The response centers of AC neurons of the mice in MK-801 group were scattered over a wider range of auditory space; the sizes of auditory spatial response area was bigger; the best frequency of AC neurons was lower; the width of tuning curve was wider; and the QndB value was smaller than that of the neurons in the other two groups.The result suggests that the auditory spatial sensitivity of AC neurons of the mice in MK-801 group is much poorer than that of control group and sham group. 3. The influence of NR2B on the development of auditory cortexUsing the histological method, we investigated the influence of NR2B on the development of auditory cortex of the adult mice in control group, sham group and MK-801 group.In MK-801 group, the auditory cortex administrated MK-801 during the critical period was much thinner than the other side of the same mouse, and the cortex of the mice in the other two groups. The cell density of the auditory cortex administrated MK-801 was also much lower than the other side of the same mouse, and the cortex of the mice in the other two groups. And we also found the auditory cortex non-administrated MK-801 during the critical period of themice in MK-801 was a little thicker than the cortex of the mice in the other two groups, while the cell density of the auditory cortex non-administrated MK-801 of the mice in MK-801 group was also a little higher than the cortex of the mice in the other two groups. It might be a kind of functional compensation during the development.The result suggests that NMDA receptor is essential in the development of auditory cortex neurons.In summary, NMDA receptor plays an important role in the postnatal development of auditory spatial sensitivity of brain neuronsin mouse.