Activation of EphB2 Forward Signaling Enhances Memory Consolidation

Cell Rep. 2018 May 15;23(7):2014-2025. doi: 10.1016/j.celrep.2018.04.042.


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.

Keywords: CREB; Eph receptor; EphB2; OptoEphB2; amygdala; fear conditioning; memory; optogenetic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Animals
  • Conditioning, Classical
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Fear
  • HEK293 Cells
  • Humans
  • Learning
  • Light
  • Male
  • Memory Consolidation*
  • Mice
  • Mice, Inbred C57BL
  • NIH 3T3 Cells
  • Optogenetics
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein Domains
  • Protein Multimerization
  • Receptor, EphB2 / chemistry
  • Receptor, EphB2 / metabolism*
  • Signal Transduction*
  • src-Family Kinases / metabolism


  • Cyclic AMP Response Element-Binding Protein
  • Phosphotyrosine
  • Receptor, EphB2
  • src-Family Kinases