title: A cluster of cholinergic premotor interneurons modulates mouse locomotor activity.
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.
authors.affiliation: Howard Hughes Medical Institute, Kavli Institute for Brain Science, Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Laskaro
authors.initials: L
authors.lastname: Zagoraiou
authors.forename: Turgay
authors.initials: T
authors.lastname: Akay
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Robert M
authors.initials: RM
authors.lastname: Brownstone
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
authors.forename: Gareth B
authors.initials: GB
authors.lastname: Miles
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000235:genetics; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002795:Choline O-Acetyltransferase / Q000172:deficiency / Q000235:genetics; D004576:Electromyography; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009415:Nerve Net / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D055749:SOXB2 Transcription Factors / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology* / Q000254:growth & development; D013569:Synapses / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism; D000097577:Homeobox Protein PITX2
chemical_list: D000109:Acetylcholine; D002795:Choline O-Acetyltransferase; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D055749:SOXB2 Transcription Factors; D014157:Transcription Factors; D050494:Vesicular Acetylcholine Transport Proteins; D016875:tau Proteins; D000097577:Homeobox Protein PITX2; C493460:Slc18a3 protein, mouse; C492175:Sox14 protein, mouse