title: Altered neuron excitability and synaptic plasticity in the cerebellar granular layer of juvenile prion protein knock-out mice with impaired motor control.
abstract: Although the role of abnormal prion protein (PrP) conformation in generating infectious brain diseases (transmissible spongiform encephalopathy) has been recognized, the function of PrP in the normal brain remains mostly unknown. In this investigation, we considered the effect of PrP gene knock-out (PrP(0/0)) on cerebellar neural circuits and in particular on granule cells, which show intense PrP expression during development and selective affinity for PrP. At the third postnatal week, when PrP expression would normally attain mature levels, PrP(0/0) mice showed low performance in the accelerating rotarod and runway tests and the functioning of 40% of granule cells was abnormal. Spikes were slow, nonovershooting, and nonrepetitive in relation with a reduction in transient inward and outward membrane currents, and also the EPSPs and EPSCs had slow kinetics. Overall, these alterations closely resembled an immature phenotype. Moreover, in slow-spiking PrP(0/0) granule cells, theta-burst stimulation was unable to induce any long-term potentiation. This profound impairment in synaptic excitation and plasticity was associated with a protracted proliferation of granule cells and disappeared at P40-P50 along with the recovery of normal motor behavior (Büeler et al., 1992). These results suggest that PrP plays an important role in granule cell development eventually regulating cerebellar network formation and motor control.
authors.affiliation: Department of Molecular/Cellular Physiology and Consorzio Nazionale Interuniversitario per le Scienze Fisiche della Materia, University of Pavia, 27100 Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Prestori
authors.forename: Paola
authors.initials: P
authors.lastname: Rossi
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bearzatto
authors.forename: Jeanne
authors.initials: J
authors.lastname: Lainé
authors.forename: Daniela
authors.initials: D
authors.lastname: Necchi
authors.forename: Shyam
authors.initials: S
authors.lastname: Diwakar
authors.forename: Serge N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: Herbert
authors.initials: H
authors.lastname: Axelrad
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D002531:Cerebellum / Q000473:pathology*; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009068:Movement / Q000502:physiology; D009069:Movement Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000502:physiology; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D011328:Prions; D001973:Bromodeoxyuridine