Abstract
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.
Highlights
Moving animals face the challenge of organizing their muscular output to meet ever-changing environmental demands
We aimed to investigate whether this is true for brainstem motor neurons as well
To this end we examined the origin of C bouton synapses on motor neurons of brainstem motor nuclei, in postnatal day 25 (P25) mice, using the Pitx2::cre;Rosa.stop.tdTomato genetic scheme that enables the visualization of the somata, as well as processes and synapses of Pitx[2] neurons
Summary
Moving animals face the challenge of organizing their muscular output to meet ever-changing environmental demands. Deciphering the circuits that provide tightly controlled input to motor neurons and regulate muscle output is imperative to further our understanding of neuromuscular physiology and pathology One of these inputs is the cholinergic neuromodulation mediated by C bouton synapses[1,2,3,4,5,6]. Molecular genetics enabled us to identify the cholinergic subset (V0c) of a small interneuron population as the sole source of spinal C bouton synapses[6]. These interneurons express the transcription factor Pitx[2] and form a rostrocaudal column along the spinal cord around the central canal. C boutons and postsynaptic m2 receptors have been reported to be absent from oculomotor, trochlear, abducens nuclei and dorsal nucleus of vagus, a parasympathetic nucleus[12,29]
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