Inhibitory modulation of medial prefrontal cortical activation on lateral orbitofrontal cortex-amygdala information flow

Several neocortical projections converge onto the basolateral complex of the amygdala (BLA), including the lateral orbitofrontal cortex (lOFC) and the medial prefrontal cortex (mPFC). Lateral orbitofrontal input to the BLA is important for cue-outcome contingencies, while medial prefrontal input is essential for emotion control. In this study, we examined how the mPFC, specifically the infralimbic division of the mPFC, modulates lOFC-BLA information flow, using combined in vivo extracellular single-unit recordings and pharmacological manipulations in anaesthetized rats. We found that the majority (over 95%) of BLA neurons that responded to lOFC stimulation also responded to mPFC stimulation. Compared to basal condition, pharmacological (N-methyl-D-aspartate) or electrical activation of the mPFC exerted an inhibitory modulation of the lOFC-BLA pathway, which was reversed with intra-amyg dala blockade of GABAergic receptors with combined GABA(A) and GABA(B) antagonists (bicuculline and saclofen). Moreover, mPFC tetanus potentiated the lOFC-BLA pathway, but mPFC tetanus or low-frequency stimulation did not alter its inhibitory modulatory gating on the lOFC-BLA pathway. These results show that the mPFC potently inhibits lOFC drive of BLA neurons in a GABA-dependent manner. Our result is informative in understanding the normal and potential pathophysiological state of emotion and contingency associations regulating behaviour.