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

Eur J Neurosci. 2001 Dec;14(11):1820-6. doi: 10.1046/j.0953-816x.2001.01806.x.

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