Altered expression of AMPAR and NMDAR subunits in hippocampal CA1 area with contextual fear memory generalization in mice

Abstract

Objective To investigate the alteration of subunit expression of AMPAR and NMDAR in hippocampal CA1 area of mice with contextual fear memory generalization. Methods 35 male C57BL/6 mice, aged 8 weeks, were involved in the experiment.Seven mice were randomly selected as the naive group, which didn't receive the behavioral training.28 mice experienced the context fear conditioning and contextual shift task were divided into generalization group and non generalization group according to the result.Then Western blot was used to measure the expression of AMPAR and NMDAR subunits in CA1 in the naive group, non generalization group and generalization group. Results (1)Seven mice (discrimination ratio: 0.52±0.08) showed contextual generalization when undergoing the same stress level, while the other 21 mice (discrimination ratio: 0.75±0.07) didn’t (P 0.05). (3)NR1 subunit was similar in the three groups(P>0.05). NR2A expression was significantly increased in the non generalization group(1.11±0.20) and generalization group (1.09±0.20 ) compared with that in the naive group(0.95±0.17) (both P<0.05). The expression of NR2B was significantly increased in generalization group(1.05±0.17) compared with that in the naive group(0.83±0.19) and non generalization group(0.80±0.14 )(both P<0.05). The ratio of NR2A/NR2B was significantly increased in non generalization group(1.23±0.25) compared with that in the naive group(0.89±0.31) and generalization group (0.86±0.17)(both P<0.05). Conclusion (1)Only part of the individuals show contextual fear memory generalization after the same stress, and this contextual generalization progress is not related to the acquisition of context fear memory.(2)There is no significant change in expression of AMPAR subunits in CA1 of mice with the contextual generalization.The rise of NR2B and the decline of ratio of NR2A/NR2B are the main changes, suggesting that consequently the alternation of synaptic plasticity maybe one of the mechanisms of contextual fear memory generalization. Key words: Contextual fear memory; Generalization; AMPA receptors; NMDA receptors