Intermediate-Term Memory for Site-Specific Sensitization in Aplysia is Maintained by Persistent Activation of Protein Kinase C

Michael A. Sutton, Martha W. Bagnall, Shiv K. Sharma, Justin Shobe, Thomas J. Carew

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia. In this system, training with a single tail shock normally induces short-term memory (< 30 min) for sensitization of tail-elicited siphon withdrawal, whereas repeated spaced shocks induce both intermediate-term memory (ITM) (>90 min) and long-term memory (>24 hr). We now show that a single tail shock can also induce ITM that is expressed selectively at the trained site (site-specific ITM). Although phenotypically similar to the form of ITM induced by repeated trials, the mechanisms by which site-specific ITM is induced and maintained are distinct. Unlike repeated-trial ITM, site-specific ITM requires neither protein synthesis nor PKA activity for induction or maintenance. Rather, the induction of site-specific ITM requires calpain-dependent proteolysis of activated PKC, yielding a persistently active PKC catalytic fragment (PKM) that also serves to maintain the memory in the intermediate-term temporal domain. Thus, two unique forms of ITM that have different induction requirements also use distinct molecular mechanisms for their maintenance.

Original languageEnglish
Pages (from-to)3600-3609
Number of pages10
JournalJournal of Neuroscience
Volume24
Issue number14
DOIs
StatePublished - Apr 7 2004
Externally publishedYes

Keywords

  • Calpain
  • Learning
  • PKA
  • PKM
  • Protein synthesis
  • Proteolysis
  • Synaptic facilitation

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