Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 4 Soranou Ephessiou Str., 11527, Athens, Greece.
Division of Animal and Human Physiology, Department of Biology, National & Kapodistrian University of Athens, Panepistimiopolis, Ilisia, Greece.
Sci Rep. 2019 Mar 20;9(1):4936. doi: 10.1038/s41598-019-39996-4.
Cholinergic neuromodulation has been described throughout the brain and has been implicated in various functions including attention, food intake and response to stress. Cholinergic modulation is also thought to be important for regulating motor systems, as revealed by studies of large cholinergic synapses on spinal motor neurons, called C boutons, which seem to control motor neuron excitability in a task-dependent manner. C boutons on spinal motor neurons stem from spinal interneurons that express the transcription factor Pitx2. C boutons have also been identified on the motor neurons of specific cranial nuclei. However, the source and roles of cranial C boutons are less clear. Previous studies suggest that they originate from Pitx2+ and Pitx2- neurons, in contrast to spinal cord C boutons that originate solely from Pitx2 neurons. Here, we address this controversy using mouse genetics, and demonstrate that brainstem C boutons are Pitx2+ derived. We also identify new Pitx2 populations and map the cholinergic Pitx2 neurons of the mouse brain. Taken together, our data present important new information about the anatomical organization of cholinergic systems which impact motor systems of the brainstem. These findings will enable further analyses of the specific roles of cholinergic modulation in motor control.
胆碱能神经调节作用在大脑中被广泛描述，并被认为与各种功能有关，包括注意力、食物摄入和应激反应。胆碱能调节也被认为对调节运动系统很重要，这一点从对脊髓运动神经元上大型胆碱能突触的研究中可以看出，这些突触被称为 C 末梢，它们似乎以任务依赖的方式控制运动神经元的兴奋性。脊髓运动神经元上的 C 末梢来源于表达转录因子 Pitx2 的脊髓中间神经元。特定颅神经核的运动神经元上也发现了 C 末梢。然而，颅 C 末梢的来源和作用尚不清楚。先前的研究表明，它们起源于 Pitx2+ 和 Pitx2-神经元，而与脊髓 C 末梢不同，后者仅起源于 Pitx2 神经元。在这里，我们使用小鼠遗传学解决了这一争议，并证明脑干部位的 C 末梢来源于 Pitx2+ 神经元。我们还鉴定了新的 Pitx2 种群，并绘制了小鼠大脑中的胆碱能 Pitx2 神经元图谱。总之，我们的数据提供了关于影响脑干运动系统的胆碱能系统解剖组织的重要新信息。这些发现将为进一步分析胆碱能调节在运动控制中的特定作用提供依据。
