Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland.
Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Nature. 2017 Nov 16;551(7680):373-377. doi: 10.1038/nature24064. Epub 2017 Oct 23.
Locomotion is a universal behaviour that provides animals with the ability to move between places. Classical experiments have used electrical microstimulation to identify brain regions that promote locomotion, but the identity of neurons that act as key intermediaries between higher motor planning centres and executive circuits in the spinal cord has remained controversial. Here we show that the mouse caudal brainstem encompasses functionally heterogeneous neuronal subpopulations that have differential effects on locomotion. These subpopulations are distinguishable by location, neurotransmitter identity and connectivity. Notably, glutamatergic neurons within the lateral paragigantocellular nucleus (LPGi), a small subregion in the caudal brainstem, are essential to support high-speed locomotion, and can positively tune locomotor speed through inputs from glutamatergic neurons of the upstream midbrain locomotor region. By contrast, glycinergic inhibitory neurons can induce different forms of behavioural arrest mapping onto distinct caudal brainstem regions. Anatomically, descending pathways of glutamatergic and glycinergic LPGi subpopulations communicate with distinct effector circuits in the spinal cord. Our results reveal that behaviourally opposing locomotor functions in the caudal brainstem were historically masked by the unexposed diversity of intermingled neuronal subpopulations. We demonstrate how specific brainstem neuron populations represent essential substrates to implement key parameters in the execution of motor programs.
运动是一种普遍的行为,使动物能够在不同的地方之间移动。经典的实验已经使用电微刺激来识别促进运动的大脑区域,但作为高级运动规划中心和脊髓执行电路之间的关键中介的神经元的身份仍然存在争议。在这里,我们表明,小鼠的脑桥尾部包含功能上不同的神经元亚群,这些亚群对运动有不同的影响。这些亚群可以通过位置、神经递质身份和连接来区分。值得注意的是,位于脑桥尾部的小区域外侧巨细胞旁核(LPGi)内的谷氨酸能神经元对于支持高速运动是必不可少的,并且可以通过来自上游中脑运动区域的谷氨酸能神经元的输入来积极调节运动速度。相比之下,甘氨酸能抑制性神经元可以诱导不同形式的行为抑制,映射到不同的脑桥尾部区域。在解剖学上,谷氨酸能和甘氨酸能 LPGi 亚群的下行通路与脊髓中的不同效应器回路进行交流。我们的结果表明,脑桥尾部具有运动功能的行为对立,在历史上被混杂的神经元亚群的未暴露多样性所掩盖。我们展示了特定的脑干神经元群体如何代表实现运动程序执行的关键参数的重要基质。