Role Of NR2A Subunit In Mouse Prefrontal Cortex-related Functions

Prefrontal cortex (PFC) plays an important role in working memory, attention regulation and behavioral inhibition, and its functions are highly correlated with N-methyl-D-aspartate (NMDA) receptors. Apart from the NR1subunit, which is the obligatory subunit for a functional NMDA receptor, NR2A and NR2B subunits are predominant in the forebrain to form NMDA receptors. NR2A-and NR2B-NMDA receptors have distinct characteristics in channel kinetics, therefore it is believed that these two subunits are involved in the regulation of NMDA receptor functions. Studies have shown that overexpression of NR2B subunit in the forebrain enhances memory, and facilitates long-term potentiation (LTP) in hippocampal CA3-CA1and medial prefrontal Ⅴ-Ⅱ pathways in mice. However, the effects of NR2A overexpression on memory and synaptic plasticity in mice are not fully understood. In order to investigate the role of NR2A subunit in prefrontal cortex-related functions, we introduced transgenic mice with forebrain overexpression of NR2A subunit, and found deficit in bidirectional long-term synaptic plasticity in the medial PFC Ⅴ-Ⅱ pathway and impairment of memory in several behavioral tests. The present study aimed to further explore the PFC-related dopamine receptor function, working memory performance and LTP in NR2A transgenic mice.The current study combined molecular and biochemical techniques along with behavioral and electrophysiological methods, employed Western blotting,[35S]GTPγS binding assay, novel object recognition, Y maze spontaneous alternation test, odor span task and field potential recordings, systematically investigated PFC-related dopamine D1receptor function, working memory and LTP in NR2A transgenic mice. The results showed normal prefrontal dopamine D1receptor function and no behavioral abnormalities in novel object recognition and Y maze spontaneous alternation test, but showed working memory deficit in the odor span task in NR2A transgenic mice. Moreover, LTP in the medial PFC Ⅱ-Ⅴ pathway was impaired in NR2A transgenic mice. These results suggest non-spatial working memory deficit in NR2A transgenic mice is associated with medial PFC LTP impairment.