Memory Retrieval Re-Activates Erk1/2 Signaling in the Same Set of CA1 Neurons Recruited During Conditioning

Neuroscience. 2018 Feb 1;370:101-111. doi: 10.1016/j.neuroscience.2017.03.034. Epub 2017 Mar 31.


The hippocampus enables a range of behaviors through its intrinsic circuits and concerted actions with other brain regions. One such important function is the retrieval of episodic memories. How hippocampal cells support retrieval of contextual fear memory remains largely unclear. Here we monitored phospho-activation of extracellular-regulated kinase (Erk1/2) across neuronal populations of the hippocampus to find that CA1 pyramidal neurons, but not cells in CA3 or dentate gyrus, specifically respond to retrieval of an aversive context. In contrast, retrieval of a neutral context that fails to elicit a threat response did not activate Erk1/2. Moreover, retrieval preferentially re-activated Erk1/2 in the same set of CA1 neurons previously activated during conditioning in a context-specific manner. By confining drug inhibition within dorsal CA1, we established the crucial role for Erk1/2 activity in retrieval of long-term memory, as well as in amygdala activation associated with fear expression. These data provide functional evidence that Erk1/2 signaling in CA1 encodes a specific neural representation of contextual memory with emotional value.

Keywords: Erk1/2 signaling; contextual fear; hippocampus; memory retrieval; neuron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / enzymology*
  • Cells, Cultured
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fear / drug effects
  • Fear / physiology
  • Indazoles / pharmacology
  • Memory, Long-Term / drug effects
  • Memory, Long-Term / physiology
  • Mental Recall / drug effects
  • Mental Recall / physiology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / enzymology*
  • Piperazines / pharmacology


  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Enzyme Inhibitors
  • Indazoles
  • Piperazines
  • SCH772984
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases