Dopamine across timescales and cell types: Relevance for phenotypes in Parkinson's disease progression

Dopamine neurons in the substantia nigra pars compacta (SNc) synthesize and release dopamine, a critical neurotransmitter for movement and learning. SNc dopamine neurons degenerate in Parkinson's Disease (PD), causing a host of motor and non-motor symptoms. Here, we review recent conceptual advances in our basic understanding of the dopamine system – including our rapidly advancing knowledge of dopamine neuron heterogeneity – with special attention to their importance for understanding PD. In PD patients, dopamine neuron degeneration progresses from lateral SNc to medial SNc, suggesting clinically relevant heterogeneity in dopamine neurons. With technical advances in dopamine system interrogation, we can understand the relevance of this heterogeneity for PD progression and harness it to develop new treatments.