The amygdala modulates prefrontal cortex activity relative to conditioned fear

Nature. 1999 Nov 18;402(6759):294-6. doi: 10.1038/46286.


Animals learn that a tone can predict the occurrence of an electric shock through classical conditioning. Mice or rats trained in this manner display fear responses, such as freezing behaviour, when they hear the conditioned tone. Studies using amygdalectomized rats have shown that the amygdala is required for both the acquisition and expression of learned fear responses. Freezing to a conditioned tone is enhanced following damage to the dorsal part of the medial prefrontal cortex, indicating that this area may be involved in fear reduction. Here we show that prefrontal neurons reduce their spontaneous activity in the presence of a conditioned aversive tone as a function of the degree of fear. The depression in prefrontal spontaneous activity is related to amygdala activity but not to the freezing response itself. These data indicate that, in the presence of threatening stimuli, the amygdala controls both fear expression and prefrontal neuronal activity. They suggest that abnormal amygdala-induced modulation of prefrontal neuronal activity may be involved in the pathophysiology of certain forms of anxiety disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / physiology*
  • Animals
  • Conditioning, Classical
  • Electrodes, Implanted
  • Fear / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / physiology
  • Prefrontal Cortex / physiology*