School of Psychology and Neuroscience, University of St Andrews, St Andrews, United Kingdom.
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Elife. 2020 Feb 21;9:e54170. doi: 10.7554/eLife.54170.
Spinal motor networks are formed by diverse populations of interneurons that set the strength and rhythmicity of behaviors such as locomotion. A small cluster of cholinergic interneurons, expressing the transcription factor Pitx2, modulates the intensity of muscle activation via 'C-bouton' inputs to motoneurons. However, the synaptic mechanisms underlying this neuromodulation remain unclear. Here, we confirm in mice that Pitx2 interneurons are active during fictive locomotion and that their chemogenetic inhibition reduces the amplitude of motor output. Furthermore, after genetic ablation of cholinergic Pitx2 interneurons, M2 receptor-dependent regulation of the intensity of locomotor output is lost. Conversely, chemogenetic stimulation of Pitx2 interneurons leads to activation of M2 receptors on motoneurons, regulation of Kv2.1 channels and greater motoneuron output due to an increase in the inter-spike afterhyperpolarization and a reduction in spike half-width. Our findings elucidate synaptic mechanisms by which cholinergic spinal interneurons modulate the final common pathway for motor output.
脊髓运动网络由多种中间神经元组成，这些神经元设定了运动等行为的强度和节律。一小群表达转录因子 Pitx2 的胆碱能中间神经元通过“C-末梢”输入到运动神经元来调节肌肉激活的强度。然而，这种神经调制的突触机制仍不清楚。在这里，我们在小鼠中证实，Pitx2 中间神经元在虚构的运动中活跃，其化学遗传抑制降低了运动输出的幅度。此外，在胆碱能 Pitx2 中间神经元被基因敲除后，M2 受体对运动输出强度的调节就会丧失。相反，Pitx2 中间神经元的化学遗传刺激导致运动神经元上 M2 受体的激活、Kv2.1 通道的调节以及由于峰后超极化的增加和峰半宽度的减小而导致运动神经元输出的增加。我们的研究结果阐明了胆碱能脊髓中间神经元调节运动输出最终共同途径的突触机制。
