The long-term environmentally selective expression of Arc in the rodent dentate gyrus is attenuated in aged rats.
1. Sackler Inst. NYU, New York, NY;
2. ARL NSMA
3. Evelyn F. McKnight Brain Inst., Univ. Arizona, Tucson, AZ;
4. Neurosci. and Neurol., Johns Hopkins Univ., Baltimore, MD
Following spatial behavioral experience, hippocampal cells express the activity-regulated, immediate early gene Arc in an environment-specific manner, and in similar proportions to cells exhibiting electrophysiologically recorded place fields under comparable conditions. While this is also true of the dentate gyrus (DG), the response of this region to spatial processing is unique in that Arc expression occurs in two stages: an initial environment-specific pattern of Arc expression restricted to the dorsal blade of the DG that remains persistently up-regulated for several hours (see Chawla et al., this session); as well as a late-emerging response in the ventral blade which appears ~6 hours following spatial experience. While it has been shown that Arc expression immediately following spatial processing is dramatically reduced in aged animals specifically in the DG, it remains unknown whether this deficit persists at long delays. By using in situ hybridization to map Arc expression in young and old rats 8 hours following exploration of a novel environment, we show that the previously observed deficit in Arc expression in the dorsal blade of the DG following spatial processing persists at long delays, and that the late-emerging response of the ventral blade is similarly attenuated in aged animals. Moreover, the degree of attenuation in both regions correlates with individual behavioral deficits in the Morris Swim Task. These data (a) suggest that both the upper and lower blades of the DG show impaired behaviorally-induced Arc expression; (b) suggest that neurons of both regions support plastic networks that are critical for spatial learning, and (c) confirm that the DG is a major locus of hippocampal dysfunction in normal aging.
Grant/Other Support: AG009219; McKnight Brain Research Foundation; state of Arizona and ADHS; NSERC
Keyword (Complete): aging; immediate-early gene; memory impairment; hippocampus