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Abstract
Mammalian motor programs are controlled by networks of spinal interneurons that set
the rhythm and intensity of motor neuron firing. Motor neurons have long been known
to receive prominent "C bouton" cholinergic inputs from spinal interneurons, but the
source and function of these synaptic inputs have remained obscure. We show here that
the transcription factor Pitx2 marks a small cluster of spinal cholinergic interneurons,
V0(C) neurons, that represents the sole source of C bouton inputs to motor neurons.
The activity of these cholinergic interneurons is tightly phase locked with motor
neuron bursting during fictive locomotor activity, suggesting a role in the modulation
of motor neuron firing frequency. Genetic inactivation of the output of these neurons
impairs a locomotor task-dependent increase in motor neuron firing and muscle activation.
Thus, V0(C) interneurons represent a defined class of spinal cholinergic interneurons
with an intrinsic neuromodulatory role in the control of locomotor behavior.