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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amnesia, Retrograde / chemically induced
-
Amnesia, Retrograde / metabolism
-
Amnesia, Retrograde / physiopathology
-
Animals
-
Cysteine Endopeptidases / metabolism*
-
Hippocampus / cytology
-
Hippocampus / drug effects
-
Hippocampus / metabolism*
-
Long-Term Potentiation / drug effects
-
Long-Term Potentiation / physiology*
-
Male
-
Memory / drug effects
-
Memory / physiology*
-
Multienzyme Complexes / antagonists & inhibitors
-
Multienzyme Complexes / metabolism*
-
Neurons / drug effects
-
Neurons / metabolism*
-
Peptide Hydrolases / drug effects
-
Peptide Hydrolases / metabolism
-
Proteasome Endopeptidase Complex
-
Rats
-
Rats, Wistar / anatomy & histology
-
Rats, Wistar / metabolism*
-
Synaptic Transmission / drug effects
-
Synaptic Transmission / physiology
-
Ubiquitin / metabolism*
Substances
-
Multienzyme Complexes
-
Ubiquitin
-
Peptide Hydrolases
-
Cysteine Endopeptidases
-
Proteasome Endopeptidase Complex