Selective prefrontal cortex inputs to dopamine cells: implications for schizophrenia.

Dopamine (DA) neurons in the substantia nigra (SN) and ventral tegmental area (VTA) form several projection systems with diverse functions, such as motor planning through the striatum, reward seeking via the nucleus accumbens (NAc), and cognitive control through the prefrontal cortex (PFC). Disruptions in DA cell activity profoundly impair these functions and contribute to serious clinical conditions such as Parkinson's disease and schizophrenia. DA neurons have been extensively investigated in studies detailing their anatomy, physiology, and neurochemical regulation. Moreoever, recordings from behaving animals suggest that phasic changes in DA cell firing signal expectancy or attentional shifts associated with approach/avoidance behavior. These ideas raise interesting questions regarding how DA neurons are regulated to produce such phasic signals. For example, it is not yet known how different classes of DA projection neurons are regulated by specific inputs. In the first study of its kind within the VTA, our laboratory recently demonstrated that excitatory inputs from the PFC synapse selectively onto DA neurons that project back to the PFC but not onto DA cells that project to the NAc. These findings may explain some of the unique functional properties of mesoprefrontal DA neurons. Moreover, the results are important for understanding the pathophysiology of mental disorders such as schizophrenia.