Dopamine Differentially Regulates Response Dynamics of Prefrontal Cortical Principal Neurons and Interneurons to Optogenetic Stimulation of Inputs from Ventral Tegmental Area.

Prefrontal cortex (PFC) is highly influenced by the inputs from ventral tegmental area (VTA); however, how the projection from VTA impacts PFC neurons and how the synaptically released dopamine affects PFC activity are largely unclear. Using optogenetics and electrophysiological approaches, we examined the impact of VTA stimulation on PFC principal neurons and parvalbumin-positive (PV+) interneurons and the modulatory role of dopamine. We found that the brief activation of the VTA-PFC circuit immediately induced action potential firing, which was mediated by glutamatergic transmission. However, strong stimulation of VTA gradually induced a marked and prolonged enhancement of the excitability of PFC PV+ interneurons and a modest and short-lived enhancement of the excitability of PFC principal neurons. Blocking dopamine receptors (DARs) shortened the VTA excitation of PFC PV+ interneurons and prolonged the VTA excitation of PFC principal neurons. Blocking GABAA receptors induced a similar effect as DAR antagonists in PFC principal neurons, suggesting that the dopaminergic effect is through influencing the inhibitory transmission system. These results have revealed a role of dopamine in regulating the temporal dynamics of excitation/inhibition balance in VTA-PFC circuit, which provides insights into the functional consequence of activating dopamine system in the mesocortical system.