Age-related changes in the protein and mRNA expression of some of the splice forms of the ζ1 (NR1) subunit of the NMDA receptor have been seen in mice and rats. The present study was designed to determine whether individual splice forms of the ζ1 subunit of the NMDA receptor within prefrontal/frontal cortical regions contribute to memory deficits during aging and whether experience in learning tasks can influence the expression of the splice forms. mRNA expression of 4 splice forms (ζ1-1, ζ1-3, ζ1-a and ζ1-b) and mRNA for all known splice forms (ζ1-pan) were examined by in situ hybridization. mRNA for C-terminal splice forms, ζ1-1 (+ C1 and + C2 cassettes) and ζ1-3 (+ C1 and + C2′), showed significant declines during aging in several brain regions even though overall ζ1-pan mRNA expression was not significantly affected by aging. This suggests that these splice forms are more influenced by aging than the subunit as a whole. There was an increase in the expression of ζ1-a (- N1 cassette) splice form in the behaviorally-experienced old mice relative to the younger groups. Old mice with high levels of mRNA expression for the ζ1-a splice form in orbital cortex showed the best performances in the working memory task, but the poorest performances in the cued, associative learning task. These results suggest that there is a complex interaction between ζ1 splice form expression and performance of memory tasks during aging.
Bibliographical noteFunding Information:
We sincerely acknowledge Dr. Karen Conneely for helping us with the corrections for the multiple correlation tests. This work was supported by NIH grant AG16322 to K.R.M. and P20RR16454-02 to BRIN.
- NMDA receptor
- Splice variants