Characterization of dopaminergic projections from the ventral tegmental area and the dorsal raphe nucleus to the orbital frontal cortex.

The orbitofrontal cortex (OFC) is a key node in the cortico-limbic-striatal circuitry that influences decision-making guided by the relative value of outcomes. Midbrain dopamine from either the ventral tegmental area (VTA) or the dorsal raphe nucleus (DRN) has the potential to modulate OFC neurons, however it is unknown at what concentrations these terminals release dopamine. Male and female adult DATIRES-CRE-tdTomato mice were injected with AAV2/8-EF1a-DIO-eYFP into either the DRN or VTA or the retrograde label CTB 488 in the medial or lateral OFC. We quantified co-expression of CTB 488 or eYFP with tdTomato fluorescence in VTA or DRN as well as eYFP fiber density in the medial or lateral OFC. Both VTA and DRN dopamine neurons project to either the medial or lateral OFC, with greater expression of fibers in the medial OFC. Using fast-scan cyclic voltammetry, we detected optogenetically evoked dopamine from channelrhodopsin2 (ChR2)-expressing VTA or DRN dopamine terminals in either the medial or lateral OFC. Consistent with increased fiber expression in the medial OFC, dopamine was more reliably detected in this region from optical stimulation of VTA or DRN dopamine terminals. We assessed if optical stimulation of dopamine from the VTA or DRN onto the medial OFC could alter layer V pyramidal neuronal firing; however, we did not observe a change in firing at stimulation parameters which evoked dopamine release from either projection. In summary, dopaminergic neurons from the VTA or DRN project to the OFC and release submicromolar dopamine in the medial and lateral OFC.