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The Journal of Neuroscience, May 27, 2009, 29(21):7098-7109; doi:10.1523/JNEUROSCI.1206-09.2009

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Development/Plasticity/Repair
In Mice Lacking V2a Interneurons, Gait Depends on Speed of Locomotion

Steven A. Crone,^1 * Guisheng Zhong,^2 * Ronald Harris-Warrick,² and Kamal Sharma¹

¹Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, and ²Department of Neurobiology and Behavior, Cornell University, Ithaca, New York 14853

Correspondence should be addressed to either of the following: Ronald Harris-Warrick, Department of Neurobiology and Behavior, Seeley Mudd Hall, Cornell University, Ithaca, NY 14853, Email: rmh4{at}cornell.edu; or Kamal Sharma, Department of Neurobiology, R218, Jules Knapp Center, 924, East 57th Street, University of Chicago, Chicago, IL 60637, Email: ksharma{at}bsd.uchicago.edu

Many animals are capable of changing gait with speed of locomotion. The neural basis of gait control and its dependence on speed are not fully understood. Mice normally use a single "trotting" gait while running at all speeds, either over ground or on a treadmill. Transgenic mouse mutants in which the trotting is replaced by hopping also lack a speed-dependent change in gait. Here we describe a transgenic mouse model in which the V2a interneurons have been ablated by targeted expression of diphtheria toxin A chain (DTA) under the control of the Chx10 gene promoter (Chx10::DTA mice). Chx10::DTA mice show normal trotting gait at slow speeds but transition to a galloping gait as speed increases. Although left–right limb coordination is altered in Chx10::DTA mice at fast speed, alternation of forelegs and hindlegs and the relative duration of swing and stance phases for individual limbs is unchanged compared with wild-type mice. The speed-dependent loss of left–right alternation is recapitulated during drug-induced fictive locomotion in spinal cords isolated from neonatal Chx10::DTA mice, and high-speed fictive locomotion evoked by caudal spinal cord stimulation also shows synchronous left–right bursting. These results show that spinal V2a interneurons are required for maintaining left–right alternation at high speeds. Whether animals that generate galloping or hopping gaits, characterized by synchronous movement of left and right forelegs and hindlegs, have lost or modified the function of V2a interneurons is an intriguing question.

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Received March 12, 2009; revised April 23, 2009; accepted April 25, 2009.

Correspondence should be addressed to either of the following: Ronald Harris-Warrick, Department of Neurobiology and Behavior, Seeley Mudd Hall, Cornell University, Ithaca, NY 14853, Email: rmh4{at}cornell.edu; or Kamal Sharma, Department of Neurobiology, R218, Jules Knapp Center, 924, East 57th Street, University of Chicago, Chicago, IL 60637, Email: ksharma{at}bsd.uchicago.edu

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