ARC GENE EXPRESSION IN THE ENTORHINAL CORTEX AND CA3 FIELD OF AGED RATS VERSUS ADULT RATS FOLLOWING ENVIRONMENTAL EXPLORATION

M.R. Penner¹*; H.L. Milliken¹; M.K. Chawla¹; S. Nematollahi¹; P.F. Worley²; C.A. Barnes¹

1. NSMA , Univ Arizona, Tucson, AZ, USA
2. Neurosci & Neurol, Johns Hopkins Univ, Baltimore , MD , USA

Recent evidence points to the dentate gyrus (DG) as the hippocampal structure most vulnerable to the effects of advancing age (Small et al., 2004). This structure receives direct cortical input almost exclusively from the superficial layers of the entorhinal cortex (layers II and III), and projects its output to the CA3 subregion of the hippocampus. Small et al. (2004) reported that cellular activation in the DG of aged rats was decreased following a simple spatial task, indicating sparser coding of incoming information in aged subjects. Thus, we investigated cellular activation in the entorhinal cortex and CA3 subregion (regions that are upstream or downstream of DG) of the hippocampus of memory-impaired aged and normal adult rats following exploration of a novel environment using catFISH. This technique allows inferences to be made about the activity history of single neurons up to widespread neural networks by measuring the cellular activation of Arc mRNA. We confirmed that the aged DG shows decreased cellular activation compared to the adult DG, and found no significant difference in cellular activation in area CA3. Analysis of Arc-positive neurons in the superficial layers of the entorhinal cortex, however, revealed increased cellular activation in the aged compared to the adult brains. These results demonstrate a significant change in the relationship between the quantitative expression of Arc in superficial entorhinal cortex and dentate granule cells in the aged brain. Increased cellular activation of the superficial EC is likely a result of changes in input to this structure, for example, from deep EC or other neocortical areas. This change however, is not passed onto the DG target synapse via the perforant path, perhaps as a result of an age-related decrease in perforant path collateral axons. Nevertheless, these changes may contribute to the learning and memory deficits that often accompany the aging process.

Support Contributed By: AG009219

Keywords: hippocampus, aging, behavior, fluorescence in situ hybridization