V1 and v2b interneurons secure the alternating flexor-extensor motor activity mice require for limbed locomotion.
Reciprocal activation of flexor and extensor muscles constitutes the fundamental mechanism that tetrapod vertebrates use for locomotion and limb-driven reflex behaviors. This aspect of motor coordination is controlled by inhibitory neurons in the spinal cord; however, the identity of the spinal interneurons that serve this function is not known. Here, we show that the production of an alternating flexor-extensor motor rhythm depends on the composite activities of two classes of ventrally located inhibitory neurons, V1 and V2b interneurons (INs). Abrogating V1 and V2b IN-derived neurotransmission in the isolated spinal cord results in a synchronous pattern of L2 flexor-related and L5 extensor-related locomotor activity. Mice lacking V1 and V2b inhibition are unable to articulate their limb joints and display marked deficits in limb-driven reflex movements. Taken together, these findings identify V1- and V2b-derived neurons as the core interneuronal components of the limb central pattern generator (CPG) that coordinate flexor-extensor motor activity.
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Jingming
J
Zhang
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Fundación Instituto Leloir, IIBBA-CONICET, Buenos Aires 1405, Argentina.
Guillermo M
GM
Lanuza
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Olivier
O
Britz
Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA.
Zhi
Z
Wang
Department of Neurosciences, Cell Biology, and Physiology, Wright State University, Dayton, OH 45435, USA.
Valerie C
VC
Siembab
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Ying
Y
Zhang
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Tomoko
T
Velasquez
Department of Neurosciences, Cell Biology, and Physiology, Wright State University, Dayton, OH 45435, USA; Department of Physiology, Emory University, Atlanta, GA 30322, USA.
Francisco J
FJ
Alvarez
Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA.
Eric
E
Frank
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: goulding@salk.edu.
Martyn
M
Goulding
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002772:Cholera Toxin / Q000378:metabolism; D004622:Embryo, Mammalian; D005121:Extremities / Q000502:physiology*; D007839:Functional Laterality / Q000187:drug effects / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013623:Tail / Q000294:innervation
D018377:Neurotransmitter Agents; D002772:Cholera Toxin