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

Abstract

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-amygdala blockade of GABAergic receptors with combined GABA and GABA 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.

Exploring Age-Related Changes in Resting State Functional Connectivity of the Amygdala: From Young to Middle Adulthood

“…Research combining behavioral tasks with tools such as dynamic causal modeling and Granger causality analysis may reveal directional functional connectivities of the amygdala ( Ide and Li, 2011 ; Hu et al, 2015 ; Zhang et al, 2015 ; Sato et al, 2017 ; Zhang Y. et al, 2017 ; Velichkovsky et al, 2018 ; Wang et al, 2018 ). This research may also benefit from studies combining functional and spectroscopy imaging of neurotransmitters ( Delli Pizzi et al, 2017a , b ) and animal work that employs pharmacological manipulations to investigate the neurochemical mechanisms underlying amygdala interaction with other brain regions ( Andolina et al, 2013 ; Chang and Ho, 2017 ; Chang and Grace, 2018 ).…”