title: Ubiquitin C-terminal hydrolase L3 (Uchl3) is involved in working memory.
abstract: Regulated proteolysis by the ubiquitin pathway has been implicated in control of the cell cycle, transcriptional activation, cell fate and growth, and synaptogenesis. The ubiquitin-proteasome system is involved in synaptic plasticity and is proposed to be part of a molecular switch that converts short-term synaptic potentiation to long-term changes in synaptic strength. In Aplysia, a component of the ubiquitin system termed ubiquitin C-terminal hydrolase (Ap-Uch) has been shown to be essential for long-term facilitation. To examine whether Uch plays a role in learning, memory, and synaptic plasticity in mammals, we have analyzed mice homozygous for a targeted mutation in ubiquitin C-terminal hydrolase L3 (Uchl3), an orthologue of Ap-Uch. Mice homozygous for the mutation in Uchl3 are viable, with no obvious developmental, histological, or fertility abnormalities. We demonstrate that Uchl3-/- mice have a significant learning deficit relative to wild type littermates in the spatial version of the Morris water maze and the 8-arm radial maze. Further, the impaired performance in the 8-arm radial maze of Uchl3-/- mice is due to significantly increased working memory errors. Examination of hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to underlie memory storage, revealed no significant differences in LTP in hippocampal slices from Uchl3-/- mice. Our results suggest a novel role for ubiquitin C-terminal hydrolase enzymes in mammals in spatial learning and working memory.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. marcelow@sas.upenn.edu
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Wood
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kaplan
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Brensinger
authors.forename: Wensheng
authors.initials: W
authors.lastname: Guo
authors.forename: Ted
authors.initials: T
authors.lastname: Abel
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000201:enzymology*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013028:Space Perception / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D043222:Ubiquitin Thiolesterase