Genetic Ablation of V2a Ipsilateral Interneurons Disrupts Left-Right Locomotor Coordination in Mammalian Spinal Cord

Steven A. Crone; Katharina A. Quinlan; Laskaro Zagoraiou; Steven Droho; Carlos Ernesto Restrepo; Line Lundfald; Toshiaki Endo; Jennifer Setlak; Thomas M. Jessell; Ole Kiehn; Kamal Sharma

doi:10.1016/j.neuron.2008.08.009

Genetic Ablation of V2a Ipsilateral Interneurons Disrupts Left-Right Locomotor Coordination in Mammalian Spinal Cord

Steven A. Crone, Katharina A. Quinlan, Laskaro Zagoraiou, Steven Droho, Carlos Ernesto Restrepo, Line Lundfald, Toshiaki Endo, Jennifer Setlak, Thomas M. Jessell, Ole Kiehn^*, Kamal Sharma

^*Corresponding author for this work

Neuroscience

Research output: Contribution to journal › Article › peer-review

263 Scopus citations

Abstract

The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways.

Original language	English (US)
Pages (from-to)	70-83
Number of pages	14
Journal	Neuron
Volume	60
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2008.08.009
State	Published - Oct 9 2008

Funding

S.A.C. is supported by a postdoctoral fellowship from the Christopher and Dana Reeve Foundation and S.D. by a graduate training grant from MGCB, University of Chicago. L.Z. was supported by a Helen Hay Whitney Fellowship. This research was supported by NIH grants to O.K. (R01 NS40795-05) and K.S. (R01 NS045106), Wings for Life (O.K.), U.S. Friends of Karolinska (O.K.), Söderbergs Foundation (O.K.), the Swedish Medical Research Council (O.K.), Brain Research Foundation (K.S.), Paralyzed Veterans of America (K.S.), and the European Union (FP7; O.K. and T.M.J.). T.M.J. is an investigator of the Howard Hughes Medical Institute and is supported by grants from the Wellcome Trust, The Harold and Leila Mathers Foundation, and Project ALS. We thank members of the Kiehn and Sharma labs and Dr. Ronald Harris-Warrick for comments on data and on a previous version of this manuscript. We would also like to thank Drs. M. Tresch and C.J. Heckman for their input and making lab resources available for parts of the reported experiments.

Keywords

CELLBIO
DEVBIO
MOLNEURO

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2008.08.009

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title = "Genetic Ablation of V2a Ipsilateral Interneurons Disrupts Left-Right Locomotor Coordination in Mammalian Spinal Cord",

abstract = "The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways.",

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author = "Crone, {Steven A.} and Quinlan, {Katharina A.} and Laskaro Zagoraiou and Steven Droho and Restrepo, {Carlos Ernesto} and Line Lundfald and Toshiaki Endo and Jennifer Setlak and Jessell, {Thomas M.} and Ole Kiehn and Kamal Sharma",

note = "Funding Information: S.A.C. is supported by a postdoctoral fellowship from the Christopher and Dana Reeve Foundation and S.D. by a graduate training grant from MGCB, University of Chicago. L.Z. was supported by a Helen Hay Whitney Fellowship. This research was supported by NIH grants to O.K. (R01 NS40795-05) and K.S. (R01 NS045106), Wings for Life (O.K.), U.S. Friends of Karolinska (O.K.), S{\"o}derbergs Foundation (O.K.), the Swedish Medical Research Council (O.K.), Brain Research Foundation (K.S.), Paralyzed Veterans of America (K.S.), and the European Union (FP7; O.K. and T.M.J.). T.M.J. is an investigator of the Howard Hughes Medical Institute and is supported by grants from the Wellcome Trust, The Harold and Leila Mathers Foundation, and Project ALS. We thank members of the Kiehn and Sharma labs and Dr. Ronald Harris-Warrick for comments on data and on a previous version of this manuscript. We would also like to thank Drs. M. Tresch and C.J. Heckman for their input and making lab resources available for parts of the reported experiments. ",

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AU - Quinlan, Katharina A.

AU - Zagoraiou, Laskaro

AU - Droho, Steven

AU - Restrepo, Carlos Ernesto

AU - Lundfald, Line

AU - Endo, Toshiaki

AU - Setlak, Jennifer

AU - Jessell, Thomas M.

AU - Kiehn, Ole

AU - Sharma, Kamal

N1 - Funding Information: S.A.C. is supported by a postdoctoral fellowship from the Christopher and Dana Reeve Foundation and S.D. by a graduate training grant from MGCB, University of Chicago. L.Z. was supported by a Helen Hay Whitney Fellowship. This research was supported by NIH grants to O.K. (R01 NS40795-05) and K.S. (R01 NS045106), Wings for Life (O.K.), U.S. Friends of Karolinska (O.K.), Söderbergs Foundation (O.K.), the Swedish Medical Research Council (O.K.), Brain Research Foundation (K.S.), Paralyzed Veterans of America (K.S.), and the European Union (FP7; O.K. and T.M.J.). T.M.J. is an investigator of the Howard Hughes Medical Institute and is supported by grants from the Wellcome Trust, The Harold and Leila Mathers Foundation, and Project ALS. We thank members of the Kiehn and Sharma labs and Dr. Ronald Harris-Warrick for comments on data and on a previous version of this manuscript. We would also like to thank Drs. M. Tresch and C.J. Heckman for their input and making lab resources available for parts of the reported experiments.

PY - 2008/10/9

Y1 - 2008/10/9

N2 - The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways.

AB - The initiation and coordination of activity in limb muscles are the main functions of neural circuits that control locomotion. Commissural neurons connect locomotor circuits on the two sides of the spinal cord, and represent the known neural substrate for left-right coordination. Here we demonstrate that a group of ipsilateral interneurons, V2a interneurons, plays an essential role in the control of left-right alternation. In the absence of V2a interneurons, the spinal cord fails to exhibit consistent left-right alternation. Locomotor burst activity shows increased variability, but flexor-extensor coordination is unaffected. Anatomical tracing studies reveal a direct excitatory input of V2a interneurons onto commissural interneurons, including a set of molecularly defined V0 neurons that drive left-right alternation. Our findings imply that the neural substrate for left-right coordination consists of at least two components; commissural neurons and a class of ipsilateral interneurons that activate commissural pathways.

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Genetic Ablation of V2a Ipsilateral Interneurons Disrupts Left-Right Locomotor Coordination in Mammalian Spinal Cord

Abstract

Funding

Keywords

ASJC Scopus subject areas

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