title: Learning, memory and long-term potentiation are altered in Nedd4 heterozygous mice.
abstract: The consolidation of short-term memory into long-term memory involves changing protein level and activity for the synaptic plasticity required for long-term potentiation (LTP). AMPA receptor trafficking is a key determinant of LTP and recently ubiquitination by Nedd4 has been shown to play an important role via direct action on the GluA1 subunit, although the physiological relevance of these findings are yet to be determined. We therefore investigated learning and memory in Nedd4(+/-) mice that have a 50% reduction in levels of Nedd4. These mice showed decreased long-term spatial memory as evidenced by significant increases in the time taken to learn the location of and subsequently find a platform in the Morris water maze. In contrast, there were no significant differences between Nedd4(+/+) and Nedd4(+/-) mice in terms of short-term spatial memory in a Y-maze test. Nedd4(+/-) mice also displayed a significant reduction in post-synaptic LTP measured in hippocampal brain slices. Immunofluorescence of Nedd4 in the hippocampus confirmed its expression in hippocampal neurons of the CA1 region. These findings indicate that reducing Nedd4 protein by 50% significantly impairs LTP and long-term memory thereby demonstrating an important role for Nedd4 in these processes.
authors.affiliation: Health Innovations Research Institute, School of Medical Science, RMIT University, P.O. Box 71, Bundoora, VIC 3083, Australia.
authors.forename: Daria
authors.initials: D
authors.lastname: Camera
authors.affiliation: Department of Physiology, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Harold A
authors.initials: HA
authors.lastname: Coleman
authors.affiliation: Department of Physiology, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Parkington
authors.affiliation: Health Innovations Research Institute, School of Medical Science, RMIT University, P.O. Box 71, Bundoora, VIC 3083, Australia.
authors.forename: Trisha A
authors.initials: TA
authors.lastname: Jenkins
authors.affiliation: Health Innovations Research Institute, School of Medical Science, RMIT University, P.O. Box 71, Bundoora, VIC 3083, Australia.
authors.forename: David V
authors.initials: DV
authors.lastname: Pow
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Natasha
authors.initials: N
authors.lastname: Boase
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, SA 5001, Australia.
authors.forename: Sharad
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Health Innovations Research Institute, School of Medical Science, RMIT University, P.O. Box 71, Bundoora, VIC 3083, Australia; Department of Physiology, School of Medical Sciences, The University of Sydney, Camperdown, NSW 2006, Australia. Electronic address: philip.poronnik@sydney.edu.au.
authors.forename: Philip
authors.initials: P
authors.lastname: Poronnik
mesh_terms: D000818:Animals; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000502:physiology*; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation; D057567:Memory, Long-Term / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D000075702:Nedd4 Ubiquitin Protein Ligases; D009474:Neurons / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D065852:Spatial Memory / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; D018091:Receptors, AMPA; D044767:Ubiquitin-Protein Ligases; C000618461:Nedd4l protein, mouse
keywords: AMPA receptor; GluA1; Long term potentiation; Memory; Nedd4; Ubiquitination