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. [Display omitted] •Activation of D1+ cells in the cuneiform or pedunculopontine nuclei evokes locomotion•Activation of D2+ cells in the cuneiform nucleus stops locomotion•Activation of D2+ cells in the pedunculopontine nucleus induces ipsilateral turning•Glutamatergic, GABAergic, and cholinergic MLR cells express dopaminergic receptors Juárez Tello et al. show that dopamine-sensitive neurons in the mesencephalic locomotor region control movement. D1 receptor-positive neurons in the cuneiform and pedunculopontine nuclei promote locomotion. D2 receptor-positive neurons in the cuneiform nucleus stop locomotion, while D2 receptor-positive neurons in the pedunculopontine nucleus induce ipsilateral turning.