The ubiquitin-proteasome cascade is required for mammalian long-term memory formation

LOPEZ-SALON, MARIELLA; ALONSO, MARIANA; VIANNA, MONICA R. M.; VIOLA, HAYDEE; MELLO E SOUZA, TADEU; IZQUIERDO, IVAN; PASQUINI, JUANA M.; MEDINA, JORGE H.

EUROPEAN JOURNAL OF NEUROSCIENCE

WILEY-BLACKWELL PUBLISHING, INC

Año: 2001 vol. 14 p. 1820 - 1826

0953-816X

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.