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Prion protein is necessary for normal synaptic function

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Abstract

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 normal2. 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 (γ-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 loss3 and neuronal degeneration seen in these diseases.

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Author notes

  1. John Collinge: To whom correspondence should be addressed.

Authors and Affiliations

  1. Prion Disease Group, Department of Biochemistry and Molecular Genetics,

    John Collinge, Katie C. L. Sidle & Mark S. Palmer

  2. Department of Physiology and Biophysics, St Mary's Hospital Medical School, Imperial College, London, W2 1PG, UK

    Miles A. Whittington & John G. R. Jefferys

  3. Department of Neurology, St Mary's Hospital, London, W2 1NY, UK

    John Collinge

  4. Department of Biochemistry, University of Bristol, School of Medical Sciences, Bristol, BS8 1TD, UK

    Corinne J. Smith & Anthony R. Clarke

Authors
  1. John Collinge
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  2. Miles A. Whittington
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  3. Katie C. L. Sidle
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  4. Corinne J. Smith
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  5. Mark S. Palmer
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  6. Anthony R. Clarke
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  7. John G. R. Jefferys
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Collinge, J., Whittington, M., Sidle, K. et al. Prion protein is necessary for normal synaptic function. Nature 370, 295–297 (1994). https://doi.org/10.1038/370295a0

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  • DOI: https://doi.org/10.1038/370295a0

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