PRION PROTEIN IS NECESSARY FOR LATENT LEARNING AND LONG-TERM-MEMORY RETENTION

1. The cellular prion protein, designated PrPc, is a key molecule in t he prion diseases but its physiological function remains unknown, To e lucidate whether PrPc plays some role in the central nervous system, w e established a line of mice in which the PrP gene had been disrupted and subsequently conducted long-term observations. 2. Performance in l atent learning and passive avoidance was evaluated using water-finding and step-through tests, respectively. 3. PrP-/- mice showed impaired performance in the water-finding test, indicating a disturbance in lat ent learning, at 23 weeks of age, In the step-through test, although t he PrP-/- mice showed normal learning ability and short-term memory re tention, they evidenced a significant disturbance in long-term memory retention. 4. These results indicate that PrPc is needed for certain t ypes of learning and memory and that the loss of function of this prot ein may contribute to the pathogenesis of prion diseases.