NEW BORN GRANULE CELLS SHOW BEHAVIORALLY-INDUCED ARC EXPRESSION: EVIDENCE FOR INTEGRATION INTO HIPPOCAMPAL NETWORKS

V. Ramirez-Amaya^1,2*; P.A. Letts¹; F.H. Gage³; P.F. Worley⁴; C.A. Barnes¹

1. NSMA , Univ Arizona, Tucson AZ, USA
2. Instit Fisiol Cel UNAM, Mexico, DF, Mexico
3. Lab Genetics, Salk Institute, La Jolla, CA, USA,
4. Neurosci & Neurol, Johns Hopkins Univ, Baltimore, MD, USA

New neurons can be born, and survive in the adult hippocampus. It has been demonstrated that newly generated granule cells (GCs) extend their axons through the mossy fiber pathway to reach CA3 pyramidal cells. Also, these new neurons exhibit electrophysiological properties similar to existing granule cells (Song et al., 2002; van Praag et al., 2002), suggesting that they may successfully integrate into hippocampal circuits. To understand if these new GCs function as part of behaviorally relevant networks, we have used a new method that allows detection of the neural ensembles activated by exploratory behavior, termed catFISH (Guzowski et al., 1999). Arc mRNA expression and translation in GCs is observed in similar proportions as the proportion of cells detected by electrophysiological recordings when animals explore an environment. Although increased c-fos immunoreactivity has been observed in new GCs (Jessberger & Kempermann, 2003), c-fos has not been linked directly to cell activity relevant to spatial behavior. Here we investigate if new born GCs express Arc in response to spatial behavior in the same manner as existing GCs. Animals were given BrdU on 5 days and 5 months later exposed to a spatial exploration experience for 5 min twice, with an intervening interval of 30 min. and sacrificed immediately after the second exploration. As expected, ~1.75% of existing GCs with no BrdU labeling express Arc protein following behavior. Mature new born granule cells (BrdU-positive) that express Arc make up 0.013% of the total granule cell population. This represents ~2.75% of total BrdU-positive cells. This suggests that new born GCs are able to express Arc in response to a behavioral experience and are, in fact, integrated into functionally relevant hippocampal networks, although with greater sensitivity than for existing GCs.

Support Contributed By: AG009219 & HFSP LT00112-2002-C

Key words: neurogenesis, immediate early genes, dentate gyrus, place cells