Projection targets of medial frontal D1DR-expressing neurons.

Prefrontal neurons expressing D1-type dopamine receptors (D1DRs) have been implicated in a variety of cognitive processes including working memory and timing. Although D1DRs are most strongly expressed on layer V/VI projection neurons, it is unknown which brain areas are specifically targeted by these projections. Here we selectively marked D1DR neurons using cre-loxP techniques with AAV carrying mCherry fluorescent protein, and traced projection targets of D1DR+ neurons in the mouse medial frontal cortex (MFC). We found relatively strong MFC D1DR+ projections to cortical areas as well as projections to basal ganglia and thalamic nuclei. We found relatively weaker MFC D1DR+ projections to the brainstem, hypothalamus, and other subcortical nuclei. These data intimate that MFC D1DR+ projections are well-positioned to powerfully influence cortical processing and have subcortical specificity. Thus MFC D1DR+ projection neurons may play a key role in tuning cortical networks during goal-directed behavior.