The Study On Function Of The NMDA Receptor In Spatial Memory Retrieval By Inducible And Reversible NR1 Knockout Mice

A large number of studies demonstrated that NMDA receptor in hippocampus synapes serves as a gating switch during the spatial memory information procession. Long-term spatial memory process, just like other types of long-term memory process, can be generally divided into four distinct stages: learning, consolidation, storage and retrieval. To study the function of NMDARs in different memory stages not only is important for understanding the molecular mechanisms of memory, but also could give some cues to elucidate the essential of memory.IT has been long known from pharmacology and genetics studies that the activities of NMDAR and synaptic plasticity depended on NMDAR are crucial in the learning, consolidation and storage stages of memory. Inhibiting the NMDAR or knockout the NR1, the core subunit of NMDAR, before learning or during the consolidation and the storage stages would produce severe amnesia for memory. But the function of NMDAR in the retrieval stage remains relatively unexplored.To examine the role of the NMDA receptor in long-term spatial retrieval stage, this paper used the third-generation knockout technique and generated the inducible, reversible, CA1-specific NR1 knockout mice (iCA1-KO) and forebrain-specific NR1 knockout mice (iFB-KO). The strategy is to use both tTA and Cre/loxp system to achieve CA1-specific/forebrain-specific, doxycycline-regulated expression of NR1-GFP transgene, thereby restoring the CA1/forebrain NMDA receptor function in the CA1/forebrain NR1 knockout mice. However, feeding the iCA1-KO and iFB-KO mice with food containing dox, a tetracycline analog with higher permeability through the blood-brain barrier, would switch off NR1-GFP transgene expression and return the mice to the NR1 knockout state in the CA1/forebrain...