PRION PROTEIN IS NECESSARY FOR NORMAL SYNAPTIC FUNCTION

THE prion diseases are neurodegenerative conditions, transmissible by inoculation, and in some cases inherited as an autosomal dominant diso rder. They include Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. The prion consists princ ipally of a post-translationally modified form of a host-encoded glyco protein (PrPc), designated PrPSc (ref. 1); the normal cellular functio n 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 norma l(2). PrP is a protein anchored to the neuronal surface by glycosylpho sphatidylinositol, suggesting a role in cell signalling or adhesion. H ere we report that hippocampal slices from PrP null mice have weakened GABA(A) (gamma-aminobutyric acid type A) receptor-mediated fast inhib ition and impaired long-term potentiation. This impaired synaptic inhi bition may be involved in the epileptiform activity seen in Creutzfeld t-Jakob disease and we argue that loss of function of PrPc may contrib ute to the early synaptic loss(3) and neuronal degeneration seen in th ese diseases.