Article abstract

Nature Neuroscience 12, 60 - 69 (2008)
Published online: 21 December 2008 | doi:10.1038/nn.2238

Olfactory behavior and physiology are disrupted in prion protein knockout mice

Claire E Le Pichon1, Matthew T Valley1, Magdalini Polymenidou2,3, Alexander T Chesler1, Botir T Sagdullaev1,3, Adriano Aguzzi2 & Stuart Firestein1

The prion protein PrPC is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp-/- mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is caused by a lack of PrPC rather than by other genetic factors. Prnp-/- mice also showed altered behavior in a second olfactory task, suggesting that the phenotype is olfactory specific. Furthermore, PrPC deficiency affected oscillatory activity in the deep layers of the main olfactory bulb, as well as dendrodendritic synaptic transmission between olfactory bulb granule and mitral cells. Notably, both the behavioral and electrophysiological alterations found in Prnp-/- mice were rescued by transgenic neuronal-specific expression of PrPC. These data suggest that PrPC is important in the normal processing of sensory information by the olfactory system.

  1. Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, New York 10027, USA.
  2. Institute of Neuropathology, University Hospital Zürich, Schmelzbergstrasse 12, 8091 Zürich, Switzerland.
  3. Present addresses: Ludwig Institute for Cancer Research, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA (M.P.) and Weill Medical College of Cornell University, 785 Mamaroneck Avenue, White Plains, New York 10605, USA (B.T.S.).

Correspondence to: Stuart Firestein1 e-mail:


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