title: Cortical gene transcription response patterns to water maze training in aged mice.
abstract: BACKGROUND
  The hippocampus mediates the acquisition of spatial memory, but the memory trace is eventually transferred to the cortex. We have investigated transcriptional activation of pathways related to cognitive function in the cortex of the aged mouse by analyzing gene expression following water maze training.
  
  
  RESULTS
  We identified genes that were differentially responsive in aged mice with accurate spatial performance during probe trials or repeated swimming sessions, relative to home cage conditions. Effective learners exhibited significantly greater activation of several pathways, such as the mitogen-activated protein kinase and insulin receptor signaling pathways, relative to swimmers. The genes encoding activity-related cytoskeletal protein (Arc) and brain-derived neurotrophic factor (BDNF) were upregulated in proficient learners, relative to swimmers and home cage controls, while the gene encoding Rho GTPase activating protein 32 (GRIT) was downregulated. We explored the regulation of Arc, BDNF, and GRIT expression in greater morphological detail using in situ hybridization. Recall during probe trials enhanced Arc expression across multiple cortical regions involved in the cognitive component of water maze learning, while BDNF expression was more homogeneously upregulated across cortical regions involved in the associational and sensorimotor aspects of water maze training. In contrast, levels of GRIT expression were uniformly reduced across all cortical regions examined.
  
  
  CONCLUSIONS
  These results suggest that cortical gene transcription is responsive to learning in aged mice that exhibit behavioral proficiency, and support a distributed hypothesis of memory storage across multiple cortical compartments.
authors.affiliation: Receptor Pharmacology Unit, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Park
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Stranahan
authors.forename: Wayne
authors.initials: W
authors.lastname: Chadwick
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Liyun
authors.initials: L
authors.lastname: Wang
authors.forename: Bronwen
authors.initials: B
authors.lastname: Martin
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Stuart
authors.initials: S
authors.lastname: Maudsley
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors