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Presynaptic inhibition of spinal sensory feedback ensures smooth movement.

Publication ,  Journal Article
Fink, AJP; Croce, KR; Huang, ZJ; Abbott, LF; Jessell, TM; Azim, E
Published in: Nature
May 1, 2014

The precision of skilled movement depends on sensory feedback and its refinement by local inhibitory microcircuits. One specialized set of spinal GABAergic interneurons forms axo-axonic contacts with the central terminals of sensory afferents, exerting presynaptic inhibitory control over sensory-motor transmission. The inability to achieve selective access to the GABAergic neurons responsible for this unorthodox inhibitory mechanism has left unresolved the contribution of presynaptic inhibition to motor behaviour. We used Gad2 as a genetic entry point to manipulate the interneurons that contact sensory terminals, and show that activation of these interneurons in mice elicits the defining physiological characteristics of presynaptic inhibition. Selective genetic ablation of Gad2-expressing interneurons severely perturbs goal-directed reaching movements, uncovering a pronounced and stereotypic forelimb motor oscillation, the core features of which are captured by modelling the consequences of sensory feedback at high gain. Our findings define the neural substrate of a genetically hardwired gain control system crucial for the smooth execution of movement.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

May 1, 2014

Volume

509

Issue

7498

Start / End Page

43 / 48

Location

England

Related Subject Headings

  • Spinal Cord
  • Presynaptic Terminals
  • Neurotransmitter Agents
  • Neural Inhibition
  • Movement
  • Motor Skills
  • Models, Neurological
  • Mice
  • Male
  • Interneurons
 

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Fink, A. J. P., Croce, K. R., Huang, Z. J., Abbott, L. F., Jessell, T. M., & Azim, E. (2014). Presynaptic inhibition of spinal sensory feedback ensures smooth movement. Nature, 509(7498), 43–48. https://doi.org/10.1038/nature13276
Fink, Andrew J. P., Katherine R. Croce, Z Josh Huang, L. F. Abbott, Thomas M. Jessell, and Eiman Azim. “Presynaptic inhibition of spinal sensory feedback ensures smooth movement.Nature 509, no. 7498 (May 1, 2014): 43–48. https://doi.org/10.1038/nature13276.
Fink AJP, Croce KR, Huang ZJ, Abbott LF, Jessell TM, Azim E. Presynaptic inhibition of spinal sensory feedback ensures smooth movement. Nature. 2014 May 1;509(7498):43–8.
Fink, Andrew J. P., et al. “Presynaptic inhibition of spinal sensory feedback ensures smooth movement.Nature, vol. 509, no. 7498, May 2014, pp. 43–48. Pubmed, doi:10.1038/nature13276.
Fink AJP, Croce KR, Huang ZJ, Abbott LF, Jessell TM, Azim E. Presynaptic inhibition of spinal sensory feedback ensures smooth movement. Nature. 2014 May 1;509(7498):43–48.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

May 1, 2014

Volume

509

Issue

7498

Start / End Page

43 / 48

Location

England

Related Subject Headings

  • Spinal Cord
  • Presynaptic Terminals
  • Neurotransmitter Agents
  • Neural Inhibition
  • Movement
  • Motor Skills
  • Models, Neurological
  • Mice
  • Male
  • Interneurons