Inhibitory Modulation of Orbitofrontal Cortex on Medial Prefrontal Cortex-Amygdala Information Flow

Cereb Cortex. 2018 Jan 1;28(1):1-8. doi: 10.1093/cercor/bhw342.


The amygdala receives cortical inputs from the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) that are believed to affect emotional control and cue-outcome contingencies, respectively. Although mPFC impact on the amygdala has been studied, how the OFC modulates mPFC-amygdala information flow, specifically the infralimbic (IL) division of mPFC, is largely unknown. In this study, combined in vivo extracellular single-unit recordings and pharmacological manipulations were used in anesthetized rats to examine how OFC modulates amygdala neurons responsive to mPFC activation. Compared with basal condition, pharmacological (N-Methyl-D-aspartate) or electrical activation of the OFC exerted an inhibitory modulation of the mPFC-amygdala pathway, which was reversed with intra-amygdala blockade of GABAergic receptors with combined GABAA and GABAB antagonists (bicuculline and saclofen). Moreover, potentiation of the OFC-related pathways resulted in a loss of OFC control over the mPFC-amygdala pathway. These results show that the OFC potently inhibits mPFC drive of the amygdala in a GABA-dependent manner; but with extended OFC pathway activation this modulation is lost. Our results provide a circuit-level basis for this interaction at the level of the amygdala, which would be critical in understanding the normal and pathophysiological control of emotion and contingency associations regulating behavior.

Keywords: amygdala; in vivo electrophysiology; medial prefrontal cortex; orbitofrontal cortex; rat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / drug effects
  • Amygdala / physiology*
  • Anesthesia
  • Animals
  • Baclofen / analogs & derivatives
  • Baclofen / pharmacology
  • Bicuculline / pharmacology
  • Electric Stimulation
  • Emotions / physiology
  • Excitatory Amino Acid Agonists / pharmacology
  • Frontal Lobe / drug effects
  • Frontal Lobe / physiology*
  • GABA Antagonists / pharmacology
  • Male
  • Microelectrodes
  • N-Methylaspartate / pharmacology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neurons / physiology*
  • Rats, Sprague-Dawley
  • Receptors, GABA / metabolism
  • gamma-Aminobutyric Acid / metabolism


  • Excitatory Amino Acid Agonists
  • GABA Antagonists
  • Receptors, GABA
  • gamma-Aminobutyric Acid
  • N-Methylaspartate
  • Baclofen
  • saclofen
  • Bicuculline