Intrinsic physiological and morphological properties of principal cells of the hippocampus and neocortex in hamsters infected with scrapie

Scrapie is a transmissible spongiform encephalopathy, or "'prion disease." We investigated the effects of intracerebral Sc237 scrapie inoculation in hamsters on the physiology and morphology of principal cells from neocortical and hippocampal slices. Scrapie inoculation resulted in increased branching of basal dendrites of hippocampal CA1 pyramidal cells (Sholl analysis), reduced amplitudes of medium and late afferhyperpolarizations (AHPs) in CA1 pyramidal cells and layer V neocortical cells, loss of frequency potentiation of depolarizing afterpotentials (DAPs), and double action potentials in synaptically evoked CA1 pyramidal cell responses. Postsynaptic double action potentials could also be evoked in normal hamster CA1 pyramidal cells by acute pharmacological block of AHPs, suggesting that the depressed AHPs in scrapie-infected hamsters caused the action potential doublets. Both the AHP and the DAP potentiations depend on increased intracellular calcium, which suggests that the underlying deficit, in hamsters infected with Sc237 scrapie, may lie in calcium entry and/or homeostasis. Fast IPSPs, passive membrane properties, and density of dendritic spines remained unchanged. These last two results differ markedly from recent studies on mice infected with ME7 scrapie, indicating diversity of pathophysiology in this group of diseases, perhaps associated with the progressive and substantial neuronal loss found in the ME7, and not the Sc237, model. (C) 1999 Academic Press.