Dopaminergic Regulation of Inhibitory and Excitatory Transmission in the Basolateral Amygdala–Prefrontal Cortical Pathway

Projections from the basolateral amygdala (BLA) and dopamine (DA) input from the ventral tegmental area (VTA) converge in the medial prefrontal cortex (mPFC), forming a neural circuit implicated in certain cognitive and emotional processes. However, the role that DA plays in modulating activity in the BLA–mPFC pathway is unknown. The present study investigated the mechanisms by which DA modulates BLA-evoked changes in mPFC neural activity, using extracellular single-unit recordings in urethane-anesthetized rats. BLA stimulation evoked two distinct types of responses in separate populations of mPFC neurons: monosynaptic, excitatory responses and, more commonly, inhibition of spontaneous firing. Stimulation of the VTA or local iontophoretic application of DA attenuated BLA-evoked inhibition of PFC neuron firing. Administration of selective DA receptor agonists revealed that these effects were mediated by D2 and D4 (but not D1) receptors. In addition, VTA stimulation or DA application attenuated BLA-evoked firing of a separate population of mPFC neurons in a frequency-dependent manner; firing evoked by higher-frequency stimulation of the BLA was less inhibited than that evoked by single-pulse stimulation. Attenuation of BLA-evoked firing was also induced by of D1 (but not D2 or D4) receptor agonists. These data indicate that dissociable DA receptor mechanisms regulate the balance of excitatory and inhibitory transmission in BLA–mPFC circuits, biasing toward an increase in the excitatory influence that the BLA exerts over populations of mPFC neurons. These findings may have important implications for understanding the pathophysiology underlying emotional and cognitive disturbances present in disorders such as depression and drug addiction.