Inhibition of calcineurin facilitates the induction of memory for sensitization in Aplysia: Requirement of mitogen-activated protein kinase

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

Research output: Contribution to journalArticle

Abstract

The induction of both synaptic plasticity and memory is thought to depend on the balance between opposing molecular regulatory factors, such as protein kinases and phosphatases. Here we show that inhibition of protein phosphatase 2B (calcineurin, CaN) facilitates the induction of intermediate-term memory (ITM) and long-term memory (LTM) for tail shock-induced sensitization in Aplysia without any effect on short-term memory. To identify the molecular cascade underlying the improvement of memory by inhibition of CaN, we examined the role of extracellular signal-regulated kinase 1/2/mitogen-activated protein kinase (MAPK). Molecular experiments revealed that one pulse of serotonin, which by itself does not activate MAPK, leads to significant MAPK activation in the sensory neurons of the pleural ganglia when CaN is inhibited. Extending these observations, behavioral experiments showed that the facilitated induction of ITM and LTM produced by CaN inhibition depends on MAPK activity. These results demonstrate: (i) that CaN acts as an inhibitory constraint in the formation of long-lasting phases of memory, and (ii) that facilitated induction of ITM and LTM by CaN inhibition requires MAPK activity.

Original languageEnglish (US)
Pages (from-to)4861-4866
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number8
DOIs
StatePublished - Apr 15 2003

Keywords

  • Extracellular signal-regulated kinase
  • Memory enhancement
  • Phosphatase

ASJC Scopus subject areas

  • General

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