Hippocampal Src kinase is required for novelty-induced enhancement of contextual fear extinction

Biochem Biophys Res Commun. 2016 Apr 15;472(4):656-61. doi: 10.1016/j.bbrc.2016.02.125. Epub 2016 Mar 9.

Abstract

Exposure to a novel environment enhances the extinction of contextual fear through the "tagging-and-capture" process. However, the underlying molecular mechanisms of novelty-induced enhancement of fear extinction are still unclear. NMDA receptor activity was recently revealed to be required for the enhancement of fear extinction caused by exposure to novelty. Src family kinases (SFKs) act as a molecular hub for regulation of NMDA receptors. We hypothesized that SFKs might be involved in novelty-induced enhancement of fear extinction. We found that the enhancement of fear extinction induced by novelty exposure is accompanied by Src kinase phosphorylation and activation in a restricted time window. Furthermore, intrahippocampal infusion of SFKs inhibitor PP2 inhibits Src kinase phosphorylation and activation, attenuates the activation of NR2B-containing NMDA receptors, and thereby reverses the enhancement of fear extinction induced by novelty exposure. These results suggested that Src kinase may serve as a behavioral tag in the procedural enhancement of fear extinction by novelty exposure.

Keywords: Fear extinction; Hippocampus; NMDA receptor; Novelty; Src kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Activation*
  • Exploratory Behavior*
  • Fear / physiology*
  • Hippocampus / physiology*
  • Male
  • Phosphorylation
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • src-Family Kinases / metabolism*

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • src-Family Kinases