The similarities and diversities of signal pathways leading to consolidation of conditioning and consolidation of extinction of fear memory

Chih Hung Lin, Shiu Hwa Yeh, Hsin Yi Lu, Po Wu Gean

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

It is generally believed that consolidation of long-term memory requires activation of protein kinases, transcription of genes, and new, protein synthesis. However, little is known about the signal cascades involved in the extinction of memory, which occurs when the conditioned stimulus is no longer followed by the unconditioned stimulus. Here, we show for the first time that an intra-amygdala injection of transcription inhibitor actinomycin D at the dose that blocked acquisition failed to affect extinction of a learned response. Conversely, protein synthesis inhibitor anisomycin blocked both acquisition and extinction. Extinction training-induced expression of calcineurin was blocked by anisomycin but not by actinomycin D. NMDA receptor antagonist, phosphatidylinositol 3-kinase (PI-3 kinase), and MAP kinase inhibitors that blocked the acquisition also blocked the extinction of conditioned fear. Likewise, PI-3 kinase inhibitor blocked fear training-induced cAMP response element-binding protein (CREB) phosphorylation as well as extinction training-induced decrease in CREB phosphorylation, the latter of which was associated with calcineurin expression and could be reversed by a specific calcineurin inhibitor. Thus, molecular processes that underlie long-term behavioral changes after acquisition and extinction share some common mechanisms and also display different characteristics.

Original languageEnglish
Pages (from-to)8310-8317
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number23
DOIs
Publication statusPublished - 2003 Sep 10

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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