The mesencephalic locomotor region (MLR) is a key midbrain center with roles in locomotion. Despite extensive studies and clinical trials aimed at therapy-resistant Parkinson’s disease (PD), debate on its function remains. Here, we reveal the existence of functionally diverse neuronal populations with distinct roles in control of body movements. We identify two spatially intermingled glutamatergic populations separable by axonal projections, mouse genetics, neuronal activity profiles, and motor functions. Most spinally projecting MLR neurons encoded the full-body behavior rearing. Loss- and gain-of-function optogenetic perturbation experiments establish a function for these neurons in controlling body extension. In contrast, Rbp4-transgene-positive MLR neurons project in an ascending direction to basal ganglia, preferentially encode the forelimb behaviors handling and grooming, and exhibit a role in modulating movement. Thus, the MLR contains glutamatergic neuronal subpopulations stratified by projection target exhibiting roles in action control not restricted to locomotion.

中脑运动区 (MLR) 是一个关键的中脑中心，在运动中发挥作用。尽管针对难治性帕金森病 (PD) 进行了广泛的研究和临床试验，但对其功能的争论仍然存在。在这里，我们揭示了功能多样的神经元群的存在，它们在控制身体运动方面具有不同的作用。我们确定了两个空间混合的谷氨酸能种群，可通过轴突投影、小鼠遗传学、神经元活动谱和运动功能分离。大多数脊柱投射的 MLR 神经元编码了全身行为的培养。功能丧失和功能获得的光遗传学扰动实验为这些神经元建立了控制身体伸展的功能。相比之下，Rbp4 转基因阳性 MLR 神经元以上升方向投射到基底神经节，优先编码前肢行为的处理和修饰，并在调节运动中发挥作用。因此，MLR 包含由投射目标分层的谷氨酸能神经元亚群，这些亚群在动作控制中的作用不限于运动。