Selective Optogenetic Stimulation of Glutamatergic, but not GABAergic, Vestibular Nuclei Neurons Induces Immediate and Reversible Postural Imbalance in Mice

Abstract

Glutamatergic and GABAergic neurons represent the main component of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei in the maintenance of gate and balance, by optogenetically stimulating the vestibular nuclei of VGluT2-cre and GAD2-cre mice. We demonstrated the VN glutamatergic, but not GABAergic subpopulation are responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface is also dramatically increased for VN-VGluT2+ animals, and rapidly come back to baseline level after stimulation, whilst it remained unchanged during all the experiment for VN-GAD2+ animals. This effect persists in condition where vestibular compensation is removed. Finally, posturolocomotor parameters such as support surface, immobility and velocity revealed the effect for VN-VGLuT2+ animals was still present immediately after stimulation, while it disappears 1h after. Overall, these results indicate a fundamental role for VN-VGluT2+ neurons in balance and posturo-locomotor functions, but not for VN-GAD2+ neurons, at least at short term. This new optogenetic approach offers to better characterize the role of glutamatergic and gabaergic functions in vestibular compensation.

Inertial Measurement of Head Tilt in Rodents: Principles and Applications to Vestibular Research

“…Direct comparison of these results with previous UVL studies is not possible as these studies used a global vestibular rating combining a series of discrete scores (obtained by the observational assessment of head tilt and circling but also of other features such as backward locomotion and postural reflexes). Our measurements are however consistent with the typical time course of this global rating in kainate- and arsanilate-induced UVL: an effect peaking in the first few hours after injection followed by an almost complete recovery within days for kainate [ 26 , 29 , 30 ] and an effect peaking in the first few days followed by partial recovery over the following weeks for arsanilate [ 31 , 32 ].…”

“…Head tilt estimation in rodents still largely relies on observational methods [ 26 , 29 , 30 , 31 , 32 ]. Compared to these approaches, IMUs can provide a comprehensive and quantitative description of head tilt both in static and dynamic conditions.…”

“…Contrary to eye movements, the assessment of head tilt in rodents has traditionally suffered from a lack of objective and quantitative measurements. In the case of UVL studies, a battery of static and dynamic features is typically rated on a discrete scale by an observer [ 26 , 29 , 30 , 31 , 32 ]. Head tilt in particular is often rated from 0 to 4 by observing the animal over a couple of minutes.…”

“…In the context of experimentally-induced vestibular lesions in rodents, head tilt has traditionally been rated on a discrete scale by an observer, offering a qualitative estimation rather than a quantitative measurement [ 26 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. In non-vestibular rodent research, approximations of head tilt angles have occasionally been calculated from photographs or single video recordings [ 36 , 37 ].…”