Olfactory behavior and physiology are disrupted in prion protein knockout mice

• Published in: Nature neuroscience Vol. 12; no. 1; pp. 60 - 69
• Main Authors: Le Pichon, Claire E, Valley, Matthew T, Polymenidou, Magdalini, Chesler, Alexander T, Sagdullaev, Botir T, Aguzzi, Adriano, Firestein, Stuart
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2009; Nature Publishing Group
• Subjects: Action Potentials; Animal Genetics and Genomics; Animals; Behavior, Animal - physiology; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Dendrites - physiology; Health aspects; Mice; Mice, Congenic; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neurobiology; Neuronal Plasticity; Neurons - metabolism; Neurosciences; Olfaction Disorders - psychology; Olfactory Bulb - metabolism; Olfactory Bulb - physiology; Olfactory cortex; Phenotype; Physiological aspects; Prion Proteins; Prions; Prions - genetics; Prions - physiology; PrPC Proteins - metabolism; PrPC Proteins - physiology; Respiration; Smell - physiology; Synaptic Transmission - physiology; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.2238

The normal physiological function of the prion protein PrP C remains unknown. Here, the authors report that PrP knockout mice show altered behavior in two olfactory tasks and that PrP deficiency affects oscillatory activity in the olfactory bulb. Both the behavioral and electrophysiological phenotypes could be rescued by transgenic neuronal-specific expression of PrP C . The prion protein PrP C 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 PrP C 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, PrP C 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 PrP C . These data suggest that PrP C is important in the normal processing of sensory information by the olfactory system.