Dissecting the diversity of midbrain dopamine neurons

•There are distinct phenotypes of midbrain dopamine neurons with segregated axonal projections. •The differential inputome for midbrain dopamine subpopulations is defined. •Optogenetic analyses of the behavioral roles of distinct midbrain dopamine neurons are discussed. Midbrain dopamine (DA) neurons are essential for controlling key functions of the brain, such as voluntary movement, reward processing, and working memory. The largest populations of midbrain DA neurons are localized in two neighboring nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA). Regardless of their different axonal projections to subcortical and cortical targets, midbrain DA neurons have traditionally been regarded as a relatively homogeneous group of neurons, with a stereotypical set of intrinsic electrophysiological properties and in vivo pattern of activity. In this review, I highlight recent data supporting an unexpected degree of diversity among these midbrain DA neurons in the mammalian brain, ranging from their developmental lineages and different synaptic connectivity to their electrophysiological properties and behavioral functions. Midbrain dopamine (DA) neurons are essential for controlling key functions of the brain, such as voluntary movement, reward processing, and working memory. The largest populations of midbrain DA neurons are localized in two neighboring nuclei, the substantia nigra (SN) and the ventral tegmental area (VTA). Regardless of their different axonal projections to subcortical and cortical targets, midbrain DA neurons have traditionally been regarded as a relatively homogeneous group of neurons, with a stereotypical set of intrinsic electrophysiological properties and in vivo pattern of activity. In this review, I highlight recent data supporting an unexpected degree of diversity among these midbrain DA neurons in the mammalian brain, ranging from their developmental lineages and different synaptic connectivity to their electrophysiological properties and behavioral functions.