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