Activation of the same mGluR5 receptors in the amygdala causes divergent effects on specific versus indiscriminate fear

Elife. 2017 May 30;6:e25665. doi: 10.7554/eLife.25665.


Although mGluR5-antagonists prevent fear and anxiety, little is known about how the same receptor in the amygdala gives rise to both. Combining in vitro and in vivo activation of mGluR5 in rats, we identify specific changes in intrinsic excitability and synaptic plasticity in basolateral amygdala neurons that give rise to temporally distinct and mutually exclusive effects on fear-related behaviors. The immediate impact of mGluR5 activation is to produce anxiety manifested as indiscriminate fear of both tone and context. Surprisingly, this state does not interfere with the proper encoding of tone-shock associations that eventually lead to enhanced cue-specific fear. These results provide a new framework for dissecting the functional impact of amygdalar mGluR-plasticity on fear versus anxiety in health and disease.

Keywords: anxiety; fear conditioning; lateral amgdala; mGluR5; neuroscience; rat; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Anxiety*
  • Behavior, Animal
  • Fear*
  • Rats
  • Receptors, Kainic Acid / agonists*


  • Gluk1 kainate receptor
  • Receptors, Kainic Acid

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.