title: Primacy of Flexor Locomotor Pattern Revealed by Ancestral Reversion of Motor Neuron Identity.
abstract: Spinal circuits can generate locomotor output in the absence of sensory or descending input, but the principles of locomotor circuit organization remain unclear. We sought insight into these principles by considering the elaboration of locomotor circuits across evolution. The identity of limb-innervating motor neurons was reverted to a state resembling that of motor neurons that direct undulatory swimming in primitive aquatic vertebrates, permitting assessment of the role of motor neuron identity in determining locomotor pattern. Two-photon imaging was coupled with spike inference to measure locomotor firing in hundreds of motor neurons in isolated mouse spinal cords. In wild-type preparations, we observed sequential recruitment of motor neurons innervating flexor muscles controlling progressively more distal joints. Strikingly, after reversion of motor neuron identity, virtually all firing patterns became distinctly flexor like. Our findings show that motor neuron identity directs locomotor circuit wiring and indicate the evolutionary primacy of flexor pattern generation.
authors.affiliation: Departments of Neuroscience and Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Kavli Institute of Brain Science, Columbia University, New York, NY 10032, USA; Department of Statistics, Center for Theoretical Neuroscience and Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA. Electronic address: tam2138@columbia.edu.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Machado
authors.affiliation: Department of Statistics, Center for Theoretical Neuroscience and Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
authors.forename: Eftychios
authors.initials: E
authors.lastname: Pnevmatikakis
authors.affiliation: Department of Statistics, Center for Theoretical Neuroscience and Grossman Center for the Statistics of Mind, Columbia University, New York, NY 10027, USA.
authors.forename: Liam
authors.initials: L
authors.lastname: Paninski
authors.affiliation: Departments of Neuroscience and Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Kavli Institute of Brain Science, Columbia University, New York, NY 10032, USA. Electronic address: tmj1@columbia.edu.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
authors.affiliation: Departments of Neuroscience and Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Kavli Institute of Brain Science, Columbia University, New York, NY 10032, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Miri
mesh_terms: D000818:Animals; D005075:Biological Evolution; D005121:Extremities / Q000294:innervation / Q000502:physiology*; D066298:In Vitro Techniques; D008124:Locomotion; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000294:innervation*; D013116:Spinal Cord / Q000502:physiology