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Nature. 2014 May 1;509(7498):43-8. doi: 10.1038/nature13276.

Presynaptic inhibition of spinal sensory feedback ensures smooth movement.

Author information

1
Howard Hughes Medical Institute, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
2
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
3
Center for Theoretical Neuroscience, Departments of Physiology and Neuroscience, Columbia University, New York, New York 10032, USA.

Abstract

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.

PMID:
24784215
PMCID:
PMC4292914
DOI:
10.1038/nature13276
[Indexed for MEDLINE]
Free PMC Article

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