Dataset Information

ROR? Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait.

ABSTRACT: Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the ROR? orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory ROR? IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of ROR? in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the ROR? inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program. VIDEO ABSTRACT.

SUBMITTER: Koch SC

PROVIDER: S-EPMC5828033 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait.

Koch Stephanie C SC Del Barrio Marta Garcia MG Dalet Antoine A Gatto Graziana G Günther Thomas T Zhang Jingming J Seidler Barbara B Saur Dieter D Schüle Roland R Goulding Martyn M

Neuron 20171207 6

Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORβ IN function result in an at ...[more]

PMID: 29224725

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Project description:Commissural interneurons (CINs) mediate interactions between rhythm-generating locomotor circuits located on each side of the spinal cord and are necessary for left-right limb coordination during locomotion. While glutamatergic V3 CINs have been implicated in left-right coordination, their functional connectivity remains elusive. Here, we addressed this issue by combining experimental and modeling approaches. We employed Sim1Cre/+; Ai32 mice, in which light-activated Channelrhodopsin-2 was selectively expressed in V3 interneurons. Fictive locomotor activity was evoked by NMDA and 5-HT in the isolated neonatal lumbar spinal cord. Flexor and extensor activities were recorded from left and right L2 and L5 ventral roots, respectively. Bilateral photoactivation of V3 interneurons increased the duration of extensor bursts resulting in a slowed down on-going rhythm. At high light intensities, extensor activity could become sustained. When light stimulation was shifted toward one side of the cord, the duration of extensor bursts still increased on both sides, but these changes were more pronounced on the contralateral side than on the ipsilateral side. Additional bursts appeared on the ipsilateral side not seen on the contralateral side. Further increase of the stimulation could suppress the contralateral oscillations by switching to a sustained extensor activity, while the ipsilateral rhythmic activity remained. To delineate the function of V3 interneurons and their connectivity, we developed a computational model of the spinal circuits consisting of two (left and right) rhythm generators (RGs) interacting via V0V, V0D, and V3 CINs. Both types of V0 CINs provided mutual inhibition between the left and right flexor RG centers and promoted left-right alternation. V3 CINs mediated mutual excitation between the left and right extensor RG centers. These interactions allowed the model to reproduce our current experimental data, while being consistent with previous data concerning the role of V0V and V0D CINs in securing left-right alternation and the changes in left-right coordination following their selective removal. We suggest that V3 CINs provide mutual excitation between the spinal neurons involved in the control of left and right extensor activity, which may promote left-right synchronization during locomotion.

Dataset Information

ROR? Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait.

Publications

RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait.

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