Projections from the rat prefrontal cortex to the ventral tegmental area: Target specificity in the synaptic associations with mesoaccumbens and mesocortical neurons

Excitatory projections from the prefrontal cortex (PFC) to the ventral tegm ental area (VTA) play an important role in regulating the activity of VTA n eurons and the extracellular levels of dopamine (DA) within forebrain regio ns. Previous investigations have demonstrated that PFC terminals synapse on the dendrites of DA and non-DA neurons in the VTA. However, the projection targets of these cells are not known. To address whether PFC afferents inn ervate different populations of VTA neurons that project to the nucleus acc umbens (NAc) or to the PFC, a triple labeling method was used that combined peroxidase markers for anterograde and retrograde tract-tracing with pre-e mbedding immunogold-silver labeling for either tyrosine hydroxylase (TH) or GABA. Within the VTA, PFC terminals formed asymmetric synapses onto dendri tic shafts that were immunoreactive for either TH or GABA. PFC terminals al so synapsed on VTA dendrites that were retrogradely labeled from the NAc or the PFC. Dendrites retrogradely labeled from the NAc and postsynaptic to P FC afferents were sometimes immunoreactive for GABA but were never TH-label ed. Conversely, dendrites retrogradely labeled from the PFC and postsynapti c to PFC afferents were sometimes immunoreactive for TH but were never GABA -labeled. These results provide the first demonstration of PFC afferents sy napsing on identified cell populations in the VTA and indicate a considerab le degree of specificity in the targets of the PFC projection. The unexpect ed finding of selective PFC synaptic input to GABA-containing mesoaccumbens neurons and DA-containing mesocortical neurons suggests novel mechanisms t hrough which the PFC can influence the activity of ascending DA and GABA pr ojections.