Gating of fear in prelimbic cortex by hippocampal and amygdala inputs

Neuron. 2012 Nov 21;76(4):804-12. doi: 10.1016/j.neuron.2012.09.028.


The prefrontal cortex (PFC) regulates emotional responses, but it is unclear how PFC integrates diverse inputs to select the appropriate response. We therefore evaluated the contribution of basolateral amygdala (BLA) and ventral hippocampus (vHPC) inputs to fear signaling in the prelimbic (PL) cortex, a PFC region critical for the expression of conditioned fear. In conditioned rats trained to press for food, BLA inactivation decreased the activity of projection cells in PL, and reduced PL conditioned tone responses. In contrast, vHPC inactivation decreased activity of interneurons in PL and increased PL conditioned tone responses. Consistent with hippocampal gating of fear after extinction, vHPC inactivation increased fear and PL pyramidal activity in extinguished, but not in conditioned, rats. These results suggest a prefrontal circuit whereby hippocampus gates amygdala-based fear. Thus, deficient hippocampal inhibition of PFC may underlie emotional disorders, especially in light of reduced hippocampal volume observed in depression and PTSD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Acoustic Stimulation
  • Action Potentials / drug effects
  • Amygdala / drug effects
  • Amygdala / physiology*
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Electroshock / methods
  • Fear* / drug effects
  • GABA-A Receptor Agonists / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Male
  • Muscimol / pharmacology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Gating / drug effects
  • Sensory Gating / physiology*
  • Statistics, Nonparametric


  • GABA-A Receptor Agonists
  • Muscimol