Protein degradation by the proteasome is required for synaptic tagging and the heterosynaptic stabilization of hippocampal late-phase long-term potentiation

F. Cai, Julietta Uta Frey, P. P. Sanna, T. Behnisch

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Activity-dependent regulation of synaptic efficacy is believed to underlie learning and memory formation. Here we show that protein degradation by the proteasome is required for the induction of the protein synthesis-dependent late-phase of long-term potentiation (late-LTP) but not for its maintenance. Proteasome activity was also key to the polarity of heterosynaptic interactions between synapses expressing synaptic plasticity and newly activated synapses. In fact, proteasome activity was required for the consolidation of an otherwise transient potentiation (early-LTP) into late-LTP by strong tetanization of a separate afferent pathway both in the "weak-before-strong" and in the "strong-before-weak" two-pathway paradigms [Frey and Morris (1997) Nature 385:533-536; Frey and Morris (1998) Neuropharmacology 37:545-552], suggesting that proteasome activity plays a role in the synaptic tagging and capture of plasticity-related proteins at stimulated synapses. Additionally, proteasome inhibition abrogated immunity against heterosynaptic depotentiation of an established late-LTP when applied during weak tetanic stimulation in the "strong-before-weak" two-pathway paradigm. Such a heterosynaptic destabilizing effect of proteasome inhibition was abolished by concomitant inhibition of N-methyl-d-aspartate (NMDA) receptors, suggesting that it is an active process. Together, these results indicate that the proteasome plays important roles in the establishment of late-LTP and in the preservation of potentiated synapses when a subsequent synaptic plasticity is induced within the same neuronal population.

Original languageEnglish (US)
Pages (from-to)1520-1526
Number of pages7
JournalNeuroscience
Volume169
Issue number4
DOIs
StatePublished - Sep 1 2010

Fingerprint

Long-Term Potentiation
Proteasome Endopeptidase Complex
Proteolysis
Synapses
Neuronal Plasticity
Long-Term Synaptic Depression
Neuropharmacology
Afferent Pathways
Immunity
Proteins
Maintenance
Learning
Population
Inhibition (Psychology)

Keywords

  • CA1
  • Heterosynaptic depotentiation
  • Hippocampus
  • Synaptic plasticity
  • Ubiquitin proteasome system

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Protein degradation by the proteasome is required for synaptic tagging and the heterosynaptic stabilization of hippocampal late-phase long-term potentiation. / Cai, F.; Frey, Julietta Uta; Sanna, P. P.; Behnisch, T.

In: Neuroscience, Vol. 169, No. 4, 01.09.2010, p. 1520-1526.

Research output: Contribution to journalArticle

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