title: The ubiquitin-proteasome cascade is required for mammalian long-term memory formation.
abstract: It has been recently demonstrated that ubiquitin-proteasome-mediated proteolysis is required for long-term synaptic facilitation in Aplysia. Here we show that the hippocampal blockade of this proteolytic pathway is also required for the formation of long-term memory in the rat. Bilateral infusion of lactacystin, a specific proteasome inhibitor, to the CA1 region caused full retrograde amnesia for a one-trial inhibitory avoidance learning when given 1, 4 or 7h, but not 10 h, after training. Proteasome inhibitor I produced similar effects. In addition, inhibitory avoidance training resulted in an increased ubiquitination and 26S proteasome proteolytic activity and a decrease in the levels of IkappaB, a substrate of the ubiquitin-proteasome cascade, in hippocampus 4 h after training. Together, these findings indicate that the ubiquitin-proteasome cascade is crucial for the establishment of LTM in the behaving animal.
authors.affiliation: Departamento de Quimica Biologica, IQUIFIB, UBA-CONICET, Argentina.
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Salon
authors.forename: M
authors.initials: M
authors.lastname: Alonso
authors.forename: M R
authors.initials: MR
authors.lastname: Vianna
authors.forename: H
authors.initials: H
authors.lastname: Viola
authors.forename: T
authors.initials: T
authors.lastname: Mello e Souza
authors.forename: I
authors.initials: I
authors.lastname: Izquierdo
authors.forename: J M
authors.initials: JM
authors.lastname: Pasquini
authors.forename: J H
authors.initials: JH
authors.lastname: Medina
mesh_terms: D000648:Amnesia, Retrograde / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D017208:Rats, Wistar / Q000033:anatomy & histology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D009097:Multienzyme Complexes; D025801:Ubiquitin; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex