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Dysfunctional dopamine (DA) signalling has been associated with a broad spectrum of neurological and psychiatric conditions, prompting investigations into how midbrain DA neuron heterogeneity may underpin this variety of behavioural symptoms. Emerging literature indeed points to functional heterogeneity even within anatomically defined DA clusters. Recognizing the need for a systematic classification scheme, we and others have used single-cell profiling to catalogue DA neurons based on their gene expression profiles. In addition, we鈥檝e developed an intersectional platform to genetically target DA neuron subpopulations, thus enabling their investigation in vivo. Using this platform, we鈥檝e revealed the unexpected complexity of ascending DAergic projections and are currently investigating the implication of this heterogeneity in behaviour and disease.

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