GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex

Dopamine-containing projections from the ventral tegmental area (VTA) to th e prefrontal cortex (PFC) have been extensively characterized since their d iscovery over 25 years ago. However, the VTA projection to the PFC also con tains a substantial nondopamine component, whose neurochemical phenotype is unknown. To examine if a portion of this nondopamine VTA projection contai ns GABA, anterograde and retrograde tract-tracing in the rat was combined w ith GABA immunocytochemistry and electron microscopy. Following injections of Fluoro-Gold CFC) into the PFC, many VTA neurons were retrogradely labele d, as visualized by immunoperoxidase staining for FG. A large portion of FG -labeled somata (58%) and dendrites (33%) within the VTA also contained imm unogold-silver labeling for GABA. These dually labeled profiles exhibited a morphology similar to dopamine-containing cells within the VTA. To confirm and extend these findings, anterograde transport of biotinylated dextran a mine (BDA) from the VTA was combined with immunogold-silver labeling for GA BA within the PFC. Consistent with the results obtained from retrograde tra cing, a portion of BDA-labeled terminals in the PFC also contained immunore activity for GABA. These dually labeled terminals formed symmetric synapses onto small caliber dendrites and dendritic spines. Some PFC dendrites cont acted by GABA-containing VTA terminals were themselves GABA-labeled. The re sults of this investigation have identified a substantial population of GAB A-containing neurons in the VTA that send axons to the PFC where they synap se on the distal processes of both pyramidal and local circuit neurons. Thi s GABA-containing mesocortical pathway may provide substrates for both inhi bitory and disinhibtory influences on PFC neuronal activity. (C) 2000 Wiley -Liss, Inc.