Gene expression profiles of brain dopamine neurons and relevance to neuropsychiatric disease

Dysfunction of dopamine neurons has been implicated in several neuropsychiatric disorders, including Parkinson's disease, addiction, bipolar disorder and depression. Recent elucidation of gene expression profiles in dopamine neuron subpopulations has shed light on the function of different groups of dopamine neurons in the CNS and on their dysfunction in disease states. In particular, concerted differences in gene expression appear to underlie the unique properties of distinct dopamine neurons. Specifically, dopamine neurons in the substantia nigra (SN), which are prone to degenerate in Parkinson's disease, express high levels of transcripts related to energy metabolism, mitochondria and phosphate signalling pathways. In contrast, ventral tegmental area (VTA) dopamine neurons prominently express genes related to synaptic plasticity and neuropeptides, suggesting intriguing mechanisms for the involvement of VTA dysfunction in addiction and mood disorders. As new functions of dopaminergic neurotransmission become clearer, continued exploration of the transcriptional neuroanatomy of these unique neurons will be vital for producing targeted, selective, and effective therapeutic agents.