Presynaptic inhibition of spinal sensory feedback ensures smooth movement

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, 508 (7498). pp. 43-48. ISSN 14764687 (ISSN)

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. © 2014 Macmillan Publishers Limited.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons > GABAergic interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > interneurons organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > presynaptic transmission organs, tissues, organelles, cell types and functions > tissues types and functions > sensory feedback organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:	Huang, Z. Josh
Communities:	CSHL labs > Huang lab
Depositing User:	Matt Covey
Date:	2014
Date Deposited:	27 May 2014 15:35
Last Modified:	07 Apr 2015 15:44
PMCID:	PMC4292914
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/30183

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