Role of EphA4 and EphrinB3 in local neuronal circuits that control walking.
Local circuits in the spinal cord that generate locomotion are termed central pattern generators (CPGs). These provide coordinated bilateral control over the normal limb alternation that underlies walking. The molecules that organize the mammalian CPG are unknown. Isolated spinal cords from mice lacking either the EphA4 receptor or its ligand ephrinB3 have lost left-right limb alternation and instead exhibit synchrony. We identified EphA4-positive neurons as an excitatory component of the locomotor CPG. Our study shows that dramatic locomotor changes can occur as a consequence of local genetic rewiring and identifies genes required for the development of normal locomotor behavior.
Kullander
Klas
K
Department of Medical Biochemistry, Gothenburg University, Medicinaregatan 9 A, 405 30 Gothenburg, Sweden. klas.kullander@medkem.gu.se
Butt
Simon J B
SJ
Lebret
James M
JM
Lundfald
Line
L
Restrepo
Carlos E
CE
Rydström
Anna
A
Klein
Rudiger
R
Kiehn
Ole
O
D000818:Animals; D001369:Axons / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004594:Electrophysiology; D036389:Ephrin-B3 / Q000235:genetics / Q000502:physiology*; D005684:Gait; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D009474:Neurons / Q000502:physiology*; D009557:Nipecotic Acids / Q000494:pharmacology; D036122:Receptor, EphA4 / Q000235:genetics / Q000502:physiology*; D012521:Sarcosine / Q000494:pharmacology; D015398:Signal Transduction; D013116:Spinal Cord / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000502:physiology; D013331:Strychnine / Q000494:pharmacology; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins; D016138:Walking
D002352:Carrier Proteins; D036389:Ephrin-B3; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; C493477:Slc17a6 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins; C030278:nipecotic acid; D036122:Receptor, EphA4; D013331:Strychnine; D001640:Bicuculline; D012521:Sarcosine