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.
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Proteasome inhibitors impair one-trial avoidance learning, spatial learning, and aversive taste memory formation.
“Early studies revealed impairments in one-trial avoidance learning, spatial learning, and aversive taste memory formation on treatment with proteasome inhibitors (Lopez-Salon et al., 2001; Artinian et al., 2008; Rodriguez-Ortiz et al., 2011).”
From Altered Phosphorylation of the Proteasome Subunit Rpt6 Has Minimal Impact on Synaptic Plasticity and Learning (2021) · cites this paper as Lopez-Salon et al., 2001
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- Authors
- Lopez‐Salon, M., Alonso, M., Vianna, M. R. M., Viola, H., E Souza, T. M., Izquierdo, I., Pasquini, J. M., & Medina, J. H.
- Affiliations
- Universidad de Buenos Aires (AR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Medina, Jorge H.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2001-12
- Volume
- 14
- Issue
- 11
- Pages
- 1820-1826
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2127639747
- Cited by
- 224
- References
- 0
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 6 · 2023: 10 · 2022: 7 · 2021: 13 · 2020: 7 · 2019: 11 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 13 · 2014: 16 · 2013: 16 · 2012: 9
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ubiquitin-proteasome system, long-term memory, hippocampus, CA1, lactacystin, proteasome inhibitors, passive avoidance, retrograde amnesia, ubiquitination, IκB, 26S proteasome, synaptic plasticity
- MeSH terms
- Amnesia, Retrograde, Animals, Cysteine Endopeptidases, Hippocampus, Male, Memory, Multienzyme Complexes, Synaptic Transmission, Neurons, Peptide Hydrolases, Rats, Wistar, Long-Term Potentiation, Ubiquitin, Proteasome Endopeptidase Complex, Rats
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