Individual dopamine midbrain neurons: functional diversity and flexibility in health and disease

Dopaminergic midbrain neurons are involved in many important brain functions including motor control, as well as emotive and cognitive tasks. They also play critical roles in major disorders likes Parkinson disease, schizophrenia, drug abuse and attention-deficit hyperactivity disorder. This bewildering diversity of distinct dopaminergic functions appears to be in contrast to the routinely assumed functional homogeneity of dopaminergic midbrain neurons at the level of individual cells. If they indeed would conform to a single stereotypical phenotype, the functional diversity of dopaminergic neurons would be predominantly mediated by their involvement in anatomically distinct subcortical and cortical neuronal networks and their distinct postsynaptic targets. However, there is increasing evidence for functional diversity as well as plasticity within the population of dopaminergic midbrain neurons. In addition, dopaminergic midbrain neurons are also not homogeneously affected by disease processes, but instead show large differences in their relative vulnerability, especially their susceptibility to cell death in Parkinson disease. Here, we review recent progress in understanding diversity and flexibility of individual dopaminergic midbrain neurons at molecular and functional levels.