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Afferents to the prefrontal cortex (PFC) from dopamine neurons in the ventral tegmental area have been implicated in working memory processes and in the pathogenesis of schizophrenia. Previous anatomical investigations have demonstrated that dopamine terminals synapse on dendritic spines and shafts of pyramidal cells in the PFC. Moreover, neurochemical and physiological studies suggest that dopamine modulates the activity of PFC neurons that project to the nucleus accumbens. However, whether this modulation involves direct synaptic input to cortico-accumbens projection neurons has not been determined. To address this question, retrograde transport of an attenuated strain of pseudorabies virus (PRV) from the nucleus accumbens was combined with immunoperoxidase labeling of tyrosine hydroxylase (TH) to identify dopamine terminals in the PFC. At survival times <48 hr, extensive dendritic distribution of immunogold labeling for PRV was observed in cortico-accumbens neurons. However, evidence consistent with trans-synaptic passage of PRV within this timeframe was observed only rarely. When examined at the electron microscopic level, immunogold labeling for PRV was localized to neuronal somata, proximal and distal dendrites, and dendritic spines. Some of these dendritic processes received symmetric synaptic input from TH-immunoreactive terminals. These data represent the first demonstration of dopamine synaptic contacts onto an identified population of pyramidal cells in the PFC. The findings have important implications for understanding how dopamine modulates cortical outflow to limbic regions in normal brain and pathological states such as schizophrenia.

Dopamine Terminals in the Rat Prefrontal Cortex Synapse on Pyramidal Cells that Project to the Nucleus Accumbens