Spinal Locomotor Circuits Develop Using Hierarchical Rules Based on Motorneuron Position and Identity.
The coordination of multi-muscle movements originates in the circuitry that regulates the firing patterns of spinal motorneurons. Sensory neurons rely on the musculotopic organization of motorneurons to establish orderly connections, prompting us to examine whether the intraspinal circuitry that coordinates motor activity likewise uses cell position as an internal wiring reference. We generated a motorneuron-specific GCaMP6f mouse line and employed two-photon imaging to monitor the activity of lumbar motorneurons. We show that the central pattern generator neural network coordinately drives rhythmic columnar-specific motorneuron bursts at distinct phases of the locomotor cycle. Using multiple genetic strategies to perturb the subtype identity and orderly position of motorneurons, we found that neurons retained their rhythmic activity-but cell position was decoupled from the normal phasing pattern underlying flexion and extension. These findings suggest a hierarchical basis of motor circuit formation that relies on increasingly stringent matching of neuronal identity and position.
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
Christopher A
CA
Hinckley
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
William A
WA
Alaynick
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
Benjamin W
BW
Gallarda
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
Marito
M
Hayashi
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
Kathryn L
KL
Hilde
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
Shawn P
SP
Driscoll
Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Joseph D
JD
Dekker
Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX 78712, USA.
Haley O
HO
Tucker
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA; Computational Neurobiology Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA.
Tatyana O
TO
Sharpee
Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines, La Jolla, CA 92037, USA. Electronic address: pfaff@salk.edu.
Samuel L
SL
Pfaff
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D063226:Central Pattern Generators / Q000166:cytology / Q000502:physiology*; D004576:Electromyography; D004622:Embryo, Mammalian; D018398:Homeodomain Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008124:Locomotion / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology*; D009415:Nerve Net / Q000502:physiology*; D010507:Periodicity; D013116:Spinal Cord / Q000166:cytology*; D018709:Statistics, Nonparametric; D014157:Transcription Factors / Q000378:metabolism
D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D014157:Transcription Factors; C084059:Hb9 protein, mouse; D002118:Calcium