Dopamine-sensitive neurons in the mesencephalic locomotor region control locomotion initiation, stop, and turns

The locomotor role of dopaminergic neurons is traditionally attributed to their ascending projections to the basal ganglia, which project to the mesencephalic locomotor region (MLR). In addition, descending dopaminergic projections to the MLR are present from basal vertebrates to mammals. However, the neurons targeted in the MLR and their behavioral role are unknown in mammals. Here, we identify genetically defined MLR cells that express D₁ or D₂ receptors and control different motor behaviors in mice. In the cuneiform nucleus, D₁-expressing neurons promote locomotion, while D₂-expressing neurons stop locomotion. In the pedunculopontine nucleus, D₁-expressing neurons promote locomotion, while D₂-expressing neurons evoke ipsilateral turns. Using RNAscope, we show that MLR dopamine-sensitive neurons comprise a combination of glutamatergic, GABAergic, and cholinergic neurons, suggesting that different neurotransmitter-based cell types work together to control distinct behavioral modules. Altogether, our study uncovers behaviorally relevant cell types in the mammalian MLR based on the expression of dopaminergic receptors.