The ubiquitin-proteasome cascade is required for mammalian long-term memory formation.
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.
Lopez-Salon
M
M
Departamento de Quimica Biologica, IQUIFIB, UBA-CONICET, Argentina.
Alonso
M
M
Vianna
M R
MR
Viola
H
H
Mello e Souza
T
T
Izquierdo
I
I
Pasquini
J M
JM
Medina
J H
JH
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*
D009097:Multienzyme Complexes; D025801:Ubiquitin; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex