MOSSY FIBER REORGANIZATION IN THE HIPPOCAMPUS OF PRION PROTEIN NULL MICE

Mice lacking prion protein (PrP-null) are resistant to transmissible s pongiform encephalopathies. However, the normal functions of this high ly conserved protein remain controversial. This study examines whether PrP-null mice develop normal neuronal pathways, specifically the mess y fibre pathway, within the hippocampus. Timm stained hippocampal sect ions from the PrP-null group had more granules than the controls in: t he granule cell layer, the inner molecular layer of the dentate gyrus, and the infrapyramidal region of CA3. This resembles the messy fibre collateral and terminal sprouting seen in certain epilepsies. The abno rmal connectivity might be predicted to promote epileptiform activity, but extracellular electrophysiological recordings from the granule ce ll layer revealed a reduced excitability in the PrP-null group, both w ith and without blockade of GABA(A) receptor-mediated inhibition. We p ropose that reorganization of neuronal circuity is a feature of PrP-nu ll mice.