TY - JOUR TI - Pitx2 cholinergic interneurons are the source of C bouton synapses on brainstem motor neurons AU - Rozani, I. AU - Tsapara, G. AU - Witts, E.C. AU - Deaville, S.J. AU - Miles, G.B. AU - Zagoraiou, L. JO - Scientific Reports PY - 2019 VL - 9 TODO - 1 SP - null PB - Nature Publishing Group SN - 2045-2322 TODO - 10.1038/s41598-019-39996-4 TODO - homeodomain protein; transcription factor; transcription factor Pitx2, animal; brain stem; cholinergic nerve cell; cytology; female; genetics; interneuron; male; metabolism; motoneuron; mouse; nerve ending; physiology; spinal cord; transgenic mouse, Animals; Brain Stem; Cholinergic Neurons; Female; Homeodomain Proteins; Interneurons; Male; Mice; Mice, Transgenic; Motor Neurons; Presynaptic Terminals; Spinal Cord; Transcription Factors TODO - 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. © 2019, The Author(s). ER -