SPATIAL-BEHAVIOR INDUCED CFOS mRNA LEVELS IN THE HIPPOCAMPUS OF YOUNG AND MEMORY IMPAIRED OLD RATS

M.K. Chawla¹*; M.R. Penner¹; V.L. Sutherland¹;
K. Olson¹; P.F. Worley²; C.A. Barnes¹

1. NSMA, Univ Arizona, Tucson, AZ, USA

2. Neurosci & Neurol, Johns Hopkins Univ, Baltimore, MD, USA

Age-related decline in cognitive function has been related to alterations in gene expression leading to changes in intracellular signaling cascades. Previous research has shown that levels of cfos mRNA is significantly higher in aged animals following long-term potentiation (Lanahan et al., 1997). Using fluorescence in situ hybridization combined with high-resolution confocal microscopy and RT-PCR we examined the dorsal hippocampal subregions of young and old rats after a brief spatial exploration or seizure. Animals were either sacrificed from their home cages (caged controls), given a 5 min exploration in a novel environment twice, separated by 20, 50, 170 or 350 min or given maximal electroconvulsive shock treatment. We found a significant increase in the number of cfos mRNA-positive cells in the hippocampus of both young and old animals following behavior; however there was no significant difference in the number of cells expressing cfos mRNA between young and old animals. Since multiplex RT-PCR can provide a quantitative estimate of RNA levels, this method was used to assess whether there was more cfos mRNA per cell in the old animals. In fact, old animals had twice the amount of cfos mRNA compared to young animals following behavior, although basal levels were similar in the two age groups. These data support the initial observation that the aged hippocampus produces more cfos mRNA following plasticity inducing stimuli (Lanahan et al., 1997), and further, provides evidence that the increase in cfos mRNA is a result of individual cells producing more mRNA, rather than more cells being transcriptionally activated by behavior in the aged brain.

Support Contributed By: AG18230, MH01565 & AG09219