Reward learning requires activity of matrix metalloproteinase-9 in the central amygdala

J Neurosci. 2013 Sep 4;33(36):14591-600. doi: 10.1523/JNEUROSCI.5239-12.2013.


Learning how to avoid danger and pursue reward depends on negative emotions motivating aversive learning and positive emotions motivating appetitive learning. The amygdala is a key component of the brain emotional system; however, an understanding of how various emotions are differentially processed in the amygdala has yet to be achieved. We report that matrix metalloproteinase-9 (MMP-9, extracellularly operating enzyme) in the central nucleus of the amygdala (CeA) is crucial for appetitive, but not for aversive, learning in mice. The knock-out of MMP-9 impairs appetitively motivated conditioning, but not an aversive one. MMP-9 is present at the excitatory synapses in the CeA with its activity greatly enhanced after the appetitive training. Finally, blocking extracellular MMP-9 activity with its inhibitor TIMP-1 provides evidence that local MMP-9 activity in the CeA is crucial for the appetitive, but not for aversive, learning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism
  • Amygdala / physiology*
  • Animals
  • Appetitive Behavior
  • Conditioning, Operant*
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Neurons / physiology
  • Reward*
  • Synapses / metabolism
  • Synapses / physiology
  • Tissue Inhibitor of Metalloproteinase-1 / pharmacology


  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse