Schematic depiction of the Mesocortical circuit.

(A) The interactions of the DLPFC and VTA in the central nervous system. DLPFC (grey region) innervates VTA nuclei (pink) located in the midbrain through corticomesencephalic glutamatergic projections (red). Reciprocally, VTA sends dopaminergic mesocortical projections (blue) to the DLPFC. (B) Detailed connection profile of various functioning modules in the mesocortical circuit. In the DLPFC, the group of pyramidal neurons, x1 (red), excites itself through recurrent connections, with synaptic strength W11, as well as excites the group of GABAergic interneurons, x2 (blue), with synaptic strength W12. In turn, the GABAergic interneurons, x2, exert a feed-back inhibition on the activity of pyramidal neurons, x1, with synaptic strength W21. Further, excitatory glutamatergic projections from pyramidal neurons, x1, excite the group of dopaminergic neurons, x3 (pink), with the efficacy W13. On excitation, the dopaminergic projections from dopaminergic neurons, x3, release dopamine (dark red) in the DLPFC with the dopamine releasability W34. The dopamine pool in the DLPFC leads to D1 receptor stimulation and, accordingly, modulates the various parameters involved in cortical dynamics. The two parameters W13 (efficacy of cortico-mesencephalic projections) and W34 (dopamine releasability) govern the efficiency of cross-talk between DLPFC and VTA, and are shown as critical tuning knobs which can be easily rotated to different levels to observe their cumulative effect on the whole circuit dynamics.