TY - JOUR
T1 - Reversible silencing of lumbar spinal interneurons unmasks a task-specific network for securing hindlimb alternation
AU - Pocratsky, Amanda M.
AU - Burke, Darlene A.
AU - Morehouse, Johnny R.
AU - Beare, Jason E.
AU - Riegler, Amberly S.
AU - Tsoulfas, Pantelis
AU - States, Gregory J.R.
AU - Whittemore, Scott R.
AU - Magnuson, David S.K.
N1 - Funding Information:
We thank Drs Tadashi Isa and Akiya Watakabe for providing the viral vector plasmids, Russell M. Howard for assistance in vector production, Christine Yarberry for surgical expertise, and Josiah Hardin for data analysis support. We thank Dr. Y. Ping Zhang and Dr. Christopher B. Shields for providing the custom-built spinal stabilizers for intraspinal injections. We also thank Dr. Andrew Todd for suggesting the goat anti-VGAT primary antibody and Dr. Ron Harris-Warrick for commentary on a previous version of this manuscript. This project utilized Kentucky Spinal Cord Injury Research Center (KSCIRC) Neuroscience core facilities that are supported by P30 GM103507 (to S.R.W.). The experiments were supported by Kentucky Spinal Cord and Head Injury Research Trust Grant 13-14, NS089324 (to D.S.K.M. and S.R.W.), Norton Healthcare, and the Commonwealth of Kentucky Challenge for Excellence (to S.R.W.).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Neural circuitry in the lumbar spinal cord governs two principal features of locomotion, rhythm and pattern, which reflect intra- and interlimb movement. These features are functionally organized into a hierarchy that precisely controls stepping in a stereotypic, speed-dependent fashion. Here, we show that a specific component of the locomotor pattern can be independently manipulated. Silencing spinal L2 interneurons that project to L5 selectively disrupts hindlimb alternation allowing a continuum of walking to hopping to emerge from the otherwise intact network. This perturbation, which is independent of speed and occurs spontaneously with each step, does not disrupt multi-joint movements or forelimb alternation, nor does it translate to a non-weight-bearing locomotor activity. Both the underlying rhythm and the usual relationship between speed and spatiotemporal characteristics of stepping persist. These data illustrate that hindlimb alternation can be manipulated independently from other core features of stepping, revealing a striking freedom in an otherwise precisely controlled system.
AB - Neural circuitry in the lumbar spinal cord governs two principal features of locomotion, rhythm and pattern, which reflect intra- and interlimb movement. These features are functionally organized into a hierarchy that precisely controls stepping in a stereotypic, speed-dependent fashion. Here, we show that a specific component of the locomotor pattern can be independently manipulated. Silencing spinal L2 interneurons that project to L5 selectively disrupts hindlimb alternation allowing a continuum of walking to hopping to emerge from the otherwise intact network. This perturbation, which is independent of speed and occurs spontaneously with each step, does not disrupt multi-joint movements or forelimb alternation, nor does it translate to a non-weight-bearing locomotor activity. Both the underlying rhythm and the usual relationship between speed and spatiotemporal characteristics of stepping persist. These data illustrate that hindlimb alternation can be manipulated independently from other core features of stepping, revealing a striking freedom in an otherwise precisely controlled system.
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U2 - 10.1038/s41467-017-02033-x
DO - 10.1038/s41467-017-02033-x
M3 - Article
C2 - 29213073
AN - SCOPUS:85038418906
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1963
ER -