title: Reducing expression of GluN1(0XX) subunit splice variants of the NMDA receptor interferes with spatial reference memory.
abstract: The GluN1 subunit of the N-methyl-D-aspartate (NMDA) receptor shows age-related changes in its expression pattern, some of which correlate with spatial memory performance in mice. Aged C57BL/6 mice show an age-related increase in mRNA expression of GluN1 subunit splice variants that lack the N terminal splice cassette, GluN1(0XX) (GluN1-a). This increase in expression is associated with good performance in reference and working memory tasks. The present study was undertaken to determine if GluN1(0XX) splice variants are required for good performance in reference memory tasks in young mice. Mice were bilaterally injected with either siRNA specific for GluN1(0XX) splice variants, control siRNA or vehicle alone into ventro-lateral orbital cortices. A fourth group of mice did not receive any injections. Starting five days post-injection, mice were tested for their performance in spatial reference memory, associative memory and cognitive flexibility tasks over four days in the Morris water maze. There was a 10-19% reduction in mRNA expression for GluN1(0XX) splice variants within the ventro-lateral orbital cortices in mice following GluN1(0XX) siRNA treatment. Declines in performance within the first half of reference memory testing were seen in the mice receiving siRNA against the GluN1(0XX) splice variants, as compared to the mice injected with control siRNA, vehicle and/or no treatment. These results suggest a role for the GluN1(0XX) splice variants in orbital regions for early acquisition and/or consolidation of spatial reference memory.
authors.affiliation: Molecular and Cellular Biology Program, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Siba R
authors.initials: SR
authors.lastname: Das
authors.forename: Ross
authors.initials: R
authors.lastname: Jensen
authors.forename: Rian
authors.initials: R
authors.lastname: Kelsay
authors.forename: Michelle
authors.initials: M
authors.lastname: Shumaker
authors.forename: Rachele
authors.initials: R
authors.lastname: Bochart
authors.forename: Brenna
authors.initials: B
authors.lastname: Brim
authors.forename: Daniel
authors.initials: D
authors.lastname: Zamzow
authors.forename: Kathy R
authors.initials: KR
authors.lastname: Magnusson
mesh_terms: D000375:Aging / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: C409466:NR1 NMDA receptor; D020033:Protein Isoforms; D021122:Protein Subunits; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate