Activation of EphB2 Forward Signaling Enhances Memory Consolidation

Jessica M. Alapin, Monica Dines, Maria Vassiliev, Tal Tamir, Alon Ram, Clifford Locke, Ji Yu, Raphael Lamprecht

Research output: Contribution to journalArticlepeer-review


EphB2 is involved in enhancing synaptic transmission and gene expression. To explore the roles of EphB2 in memory formation and enhancement, we used a photoactivatable EphB2 (optoEphB2) to activate EphB2 forward signaling in pyramidal neurons in lateral amygdala (LA). Photoactivation of optoEphB2 during fear conditioning, but not minutes afterward, enhanced long-term, but not short-term, auditory fear conditioning. Photoactivation of optoEphB2 during fear conditioning led to activation of the cAMP/Ca2+ responsive element binding (CREB) protein. Application of light to a kinase-dead optoEphB2 in LA did not lead to enhancement of long-term fear conditioning memory or to activation of CREB. Long-term, but not short-term, auditory fear conditioning memory was impaired in mice lacking EphB2 forward signaling (EphB2lacZ/lacZ). Activation of optoEphB2 in LA of EphB2lacZ/lacZ mice enhanced long-term fear conditioning memory. The present findings show that the level of EphB2 forward signaling activity during learning determines the strength of long-term memory consolidation. Alapin et al. show that activation of photoactivatable EphB2 (optoEphB2) in the lateral amygdala of mice during fear conditioning specifically enhances long-term auditory fear conditioning memory and CREB activation. However, the kinase-dead opto-EphB2 has no effects on LTM or pCREB. Photoactivation of optoEphB2 in LA of EphB2lacZ/lacZ mice enhances fear LTM.

Original languageEnglish
Pages (from-to)2014-2025
Number of pages12
JournalCell Reports
Issue number7
StatePublished - 15 May 2018

Bibliographical note

Publisher Copyright:
© 2018 The Author(s)


  • CREB
  • Eph receptor
  • EphB2
  • OptoEphB2
  • amygdala
  • fear conditioning
  • memory
  • optogenetic

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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