Summary The basal ganglia (BG) are critical for adaptive motor control, but the circuit principles underlying their pathway-specific modulation of target regions are not well understood. Here, we dissect the mechanisms underlying BG direct- and indirect-pathway-mediated control of the mesencephalic locomotor region (MLR), a brainstem target of the BG that is critical for locomotion. We optogenetically dissect the locomotor function of the three neurochemically-distinct cell types within the MLR: glutamatergic, GABAergic, and cholinergic neurons. We find that the glutamatergic subpopulation encodes locomotor state and speed, is necessary and sufficient for locomotion, and is selectively innervated by BG. We further show activation and suppression, respectively, of MLR glutamatergic neurons by direct and indirect pathways, which is required for bidirectional control of locomotion by BG circuits. These findings provide a fundamental understanding of how the BG can initiate or suppress a motor program through cell-type-specific regulation of neurons linked to specific actions.

The ability to stop ongoing movement is fundamental to animal survival. Behavioural arrest involves the hierarchical integration of information throughout the forebrain, which ultimately leads to the coordinated inhibition and activation of specific brainstem motor centres. Recent advances have shed light on multiple regions and pathways involved in this critical behavioural process. Here, we synthesize these new findings together with previous work to build a more complete understanding of the circuit mechanisms underlying suppression of ongoing action. We focus on three specific conditions leading to behavioural arrest: goal completion, fear and startle. We outline the circuitry responsible for the production of these behaviours and discuss their dysfunction in neurological disease.This article is part of the themed issue 'Movement suppression: brain mechanisms for stopping and stillness'.

Reinforcement has long been thought to require striatal synaptic plasticity. Indeed, direct striatal manipulations such as self-stimulation of direct-pathway projection neurons (dMSNs) are sufficient to induce reinforcement within minutes. However, it’s unclear what role, if any, is played by downstream circuitry. Here, we used dMSN self-stimulation in mice as a model for striatum-driven reinforcement and mapped the underlying circuitry across multiple basal ganglia nuclei and output targets. We found that mimicking the effects of dMSN activation on downstream circuitry, through optogenetic suppression of basal ganglia output nucleus substantia nigra reticulata (SNr) or activation of SNr targets in the brainstem or thalamus, was also sufficient to drive rapid reinforcement. Remarkably, silencing motor thalamus—but not other selected targets of SNr—was the only manipulation that reduced dMSN-driven reinforcement. Together, these results point to an unexpected role for basal ganglia output to motor thalamus in striatum-driven reinforcement.