A genetically defined asymmetry underlies the inhibitory control of flexor-extensor locomotor movements.

Olivier Britz,Katja S Grossmann,Jun C Kim,Simon Gosgnach,Jingming Zhang,Jason Dyck,Susan Dymecki,Martyn Goulding

doi:10.7554/elife.04718

Olivier Britz, Katja S Grossmann + Show 6 more

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https://doi.org/10.7554/elife.04718

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Abstract

V1 and V2b interneurons (INs) are essential for the production of an alternating flexor-extensor motor output. Using a tripartite genetic system to selectively ablate either V1 or V2b INs in the caudal spinal cord and assess their specific functions in awake behaving animals, we find that V1 and V2b INs function in an opposing manner to control flexor-extensor-driven movements. Ablation of V1 INs results in limb hyperflexion, suggesting that V1 IN-derived inhibition is needed for proper extension movements of the limb. The loss of V2b INs results in hindlimb hyperextension and a delay in the transition from stance phase to swing phase, demonstrating V2b INs are required for the timely initiation and execution of limb flexion movements. Our findings also reveal a bias in the innervation of flexor- and extensor-related motor neurons by V1 and V2b INs that likely contributes to their differential actions on flexion-extension movements.

Highlights

Terrestrial animals use their limbs to generate a broad array of motor behaviors, from stereotypical movements that include protective reflexes and locomotion to complex volitional tasks that are exemplified by reaching and grasping movements (Grillner, 1975; Alstermark and Isa, 2012)
It is known that reciprocal flexor–extensor motor activity is produced by inhibitory neurons in the spinal cord, many of which appear to be core components of the locomotor central pattern generator (CPG)
Efforts to define the contribution that V1 and V2b INs make to locomotion in awake behaving mice have been thwarted by an inability to selectively manipulate these cells in the spinal cord

Summary

Introduction

Terrestrial animals use their limbs to generate a broad array of motor behaviors, from stereotypical movements that include protective reflexes and locomotion to complex volitional tasks that are exemplified by reaching and grasping movements (Grillner, 1975; Alstermark and Isa, 2012). The most prominent of these are reciprocal Ia inhibitory interneurons (IaINs), which are activated by muscle spindle afferents and inhibit antagonist motor neurons. Peak IaIN activity coincides with the phase in which antagonist motor neurons are hyperpolarized (Pratt and Jordon, 1987; Geertsen et al, 2011). This activity profile is strong evidence of a central role in reciprocal inhibition. While the IbINs that are innervated by Golgi tendon organs (GTOs) generally inhibit homonymous motor neurons under non-locomotor conditions (Jankowska, 1992; Pearson and Collins, 1993), Britz et al eLife 2015;4:e04718.

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