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bioRxiv · 10.1101/2020.09.03.281980

Novel Model of Reversible Vestibular Syndrom Induced by Optogenetic Stimulation

Montardy, Q.·Mengxia, W.·Yi, T.·Liu, X.·Zheng, Z.·Besnard, S.·Tighilet, B.·Chabbert, C.·Wang, L.
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Abstract

Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular compensation was removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology. HighlightsO_LIFor the first time, Vestibular nuclei were optogenetically stimulated in free-moving animals, to asses for glutamatergic and GABAergic neurons functions in posturo-locomotor behaviors. C_LIO_LIBrief optogenetic activation of VNVGluT2+, but not VNGAD2+, induced immediate and strong postural deficit. C_LIO_LIStimulation of VNVGluT2+ neurons provoked an imbalance with continuous effect on locomotion for a short period of time after stimulation. C_LIO_LIThese results are comparable to the classical vestibular deafferentation models during their peak of deficit, and set optogenetic stimulation as a new model to study vestibular deficits. C_LI

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Montardy, Q., Mengxia, W., Yi, T., Liu, X., Zheng, Z., Besnard, S., Tighilet, B., Chabbert, C., Wang, L.. 2020-09-04. Novel Model of Reversible Vestibular Syndrom Induced by Optogenetic Stimulation. https://doi.org/10.1101/2020.09.03.281980

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