Effects of enriched environment on gene expression and signal pathways in cortex of hippocampal CA1 specific NMDAR1 knockout mice.

N-methyl-D-aspartate glutamate receptor 1 (NMDAR1) plays a pivotal role in different forms of memory. Indeed, hippocampal CA1 region specific knockout (KO) of NMDAR1 in mice showed memory impairment. Recently, it has been reported that environmental enrichment enhanced memory and rescued the memory deficits of the NMDAR1-KO mice. It is well known that cortex has synaptic connections with hippocampus and is the storage region of the brain for long-term memory. To understand the molecular mechanisms of the memory impairments in the NMDAR1-KO mice, we have examined gene expression profiles in cortex from the receptor KO mice compared to wild type mice. Furthermore, since memory deficits were rescued after exposure of the NMDAR1-KO mice to enriched environment, we also analyzed the gene expression in the cortex of the KO mice after 3 hours, 2 days and 2 weeks enrichment. We found that the expression levels of 104 genes were altered in the cortex of NMDAR1-KO mice. Environmental enrichment for 3 hours, 2 days and 2 weeks affected the expression of 45, 34 and 56 genes, respectively. Genes involved in multiple signal pathways were regulated in the NMDAR1-KO mice, such as neurotransmission, structure, transcription, protein synthesis and protein processing. It is not surprising that since enriched environment rescued the memory decline in the NMDAR1-KO mice, the expression changes of a number of genes involved in these signal pathways were recovered or even reversed after enrichment. Our results further demonstrated that reelin and Notch signal pathways could be involved in the enrichment effects on memory improvement in the KO mice.