MOLECULAR REACTIVATION OF ARC PROTEIN AFTER SPATIAL EXPLORATION

V. Ramirez-Amaya¹*; A. Vazdarjanova¹;
D.M. Mikhael¹; P.F. Worley²; C.A. Barnes¹

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

The immediate-early gene Arc is expressed in the hippocampus and neocortex after spatial exploration. Arc mRNA first appears in the nuclei of CA3, CA1 and parietal cortex (PCx) neurons within 5 min after spatial exploration and then moves to the cytoplasm after 25 min. We studied the temporal dynamics of Arc protein by exposing rats to a novel environment twice with one of 8 intervals (0.5, 1, 2, 3, 4, 6, 8 and 24 hrs) between the exposures and sacrificed them immediately after the second exposure. Fluorescence immunohistochemistry and catFISH for Arc revealed that as soon as Arc mRNA reached the cytoplasm it was reliably translated into protein, evidenced by similar proportions of Arc-positive mRNA and Arc-positive protein cells in the 0.5-hr group. The number of Arc-positive cells remained high for 2 hrs and returned to baseline by 3 hrs. Importantly, in CA3 and PCx there was a second wave of Arc expression at 8 and 24 hrs that occurred in ~50% of the originally-activated ensembles (cells double-labeled for Arc mRNA and protein), suggesting a highly specific "molecular reactivation" in these ensembles. Furthermore, the proportions of cells that express Arc protein in CA1, CA3 and PCx covaried congruently at the 24 hour time point. That is, within an individual animal, the rat that showed the lowest or highest proportions of PCx expression also tended to show the lowest or highest proportions in CA1 and CA3. These significant correlations suggest that such off-line molecular reactivation may be an anatomical signature of memory consolidation.

Support Contributed By: AG09219, HFSP LT00112-2002-C & MH64357