Venue : Centre Broca
Thesis defended in french
Léandre Lavenu
Team : Monoamines, Parkinson and Pain
IMN
Thesis directed by Pascal Fossat and Didier Le Ray
Title
Involvement of brainstem inhibitory networks in the organization of vestibulospinal reflexes
Abstract
In vertebrates, postural control of the entire body is primarily maintained by motor reflexes of vestibular origin. Excitatory vestibulospinal pathways constitute the main routes regulating these postural reflexes. Such pathways have been described in numerous vertebrate species and exhibit striking anatomical similarities even among phylogenetically distant species with markedly different biomechanical characteristics. In this thesis, we focused on two evolutionarily distant vertebrate species: the amphibian Xenopus laevis and the mammal, the mouse. Our goal was to determine whether inhibitory networks orchestrate the activity of excitatory vestibulospinal neurons, which generate postural reflexes, throughout evolution. Using various anatomical techniques, we first demonstrated that inhibitory vestibulospinal projection neurons are present in larval Xenopus, but disappear after metamorphosis. Similarly, these inhibitory neurons were not observed in adult mice, although their presence had previously been reported during the perinatal stage. In addition, we found that GABAergic and glycinergic systems are present within vestibulospinal neurons in both species, but their density varies according to developmental stage and species. We then conducted a functional study using a central nervous system (CNS) preparation from larval Xenopus. Our results show that spinal responses elicited by galvanic vestibular stimulation are modulated by GABAergic and glycinergic inhibition in distinct ways. These inhibitory effects involve both local and commissural networks. Moreover, direct stimulation of each vestibulospinal nucleus suggest that glycinergic inhibition of vestibulospinal neurons is tonic in nature. Furthermore, our findings suggest that tonic glycinergic activity is reduced through modulation by GABAergic neurons. This interaction regulates vestibulospinal neuron activity and, consequently, the amplitude of spinal reflex responses. In parallel, we examined posturo-locomotor behaviors in mice after inhibiting the activity of GABAergic neurons within the medial vestibular nucleus. Our observations indicate that head posture tone is partly controlled by this neuronal population. However, general limb mobility and overall posture remained unaffected. The results obtained in larval Xenopus highlight the crucial role of inhibitory networks in coordinating vestibulospinal activity and, consequently, in establishing proper postural reflexes. In mice, GABAergic networks also appear to play a role, particularly in maintaining head posture against gravity. The subtle differences observed between species may result from compensatory mechanisms in mice, possibly mediated by glycinergic inhibition and more complex brain structures such as the cerebellum, compared to Xenopus. Taken together, these findings provide a first step toward demonstrating the essential contribution of inhibitory networks in orchestrating vestibular reflex activity. Targeting these inhibitory pathways could represent a promising strategy for developing treatments for vestibular disorders.
Key words
Vestibulospinal, inhibition, posture, vestibular system, Xenopus laevis, mouse, reflex
Jury
Présidente : Karine Massé
Rapporteurs : Alexandra Severac-Cauquil et Frédéric Brocard
Examinateurs: Claire Wyart, Lora Sweeney et Mathieu Beraneck