Prion protein is necessary for normal synaptic function

Author(s): Collinge J, Whittington MA, Sidle KC, Smith CJ, Palmer MS, et al.


The prion diseases are neurodegenerative conditions, transmissible by inoculation, and in some cases inherited as an autosomal dominant disorder. They include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. The prion consists principally of a post-translationally modified form of a host-encoded glycoprotein (PrPC), designated PrPSc (ref. 1); the normal cellular function of PrPC is, however, unknown. Although PrP is highly conserved among mammals and widely expressed in early embryogenesis, mice homozygous for disrupted PrP genes appear developmentally and behaviourally normal. PrP is a protein anchored to the neuronal surface by glycosylphosphatidylinositol, suggesting a role in cell signalling or adhesion. Here we report that hippocampal slices from PrP null mice have weakened GABAA (gamma-aminobutyric acid type A) receptor-mediated fast inhibition and impaired long-term potentiation. This impaired synaptic inhibition may be involved in the epileptiform activity seen in Creutzfeldt-Jakob disease and we argue that loss of function of PrPC may contribute to the early synaptic loss and neuronal degeneration seen in these diseases.

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