Evolutionary and developmental neurophysiological substrates for gaze stabilization strategies during locomotion in vertebrates – Locogaze

Accurate visual information is crucial to most animals for locating food, detecting predators or mates and orienting themselves within their environment. In order to stabilize gaze and maintain visual acuity during head movements resulting from self-motion, multiple convergent sensory-motor systems are involved, including vestibulo-ocular and optokinetic reflexes, supplemented by vestibulocollic and optocollic reflexes in animals with flexible necks. By using a tractable lower vertebrate model (the amphibian Xenopus laevis) we have recently shown that in addition to these sensory feedback mechanisms, a predictive feed-forward (efference copy) signaling from the spinal locomotor pattern generator itself is also engaged in minimizing visual disturbances during locomotion. This novel concept questions the traditional view of retinal image stabilization that in vertebrates has been so far exclusively attributed to sensorimotor transformations of body/head movement-detecting signals. In this proposal, we aim to investigate within an ontogenetic and phylogenic context the cellular substrates and developmental dynamics of this newly discovered gaze-stabilizing mechanism, previously suspected but never demonstrated in higher vertebrates including humans.
Two complementary animal models (Xenopus and mouse) will be used, enabling integrative neurobiological approaches ranging from the behavioral to cellular levels. Xenopus will enable studying the developmental adaptation of this intrinsic mechanism during metamorphosis, as the animal's locomotor strategy switches from fish-like swimming to quadrupedal locomotion. Moreover, its relative simplicity compared to mammals will allow a more extensive investigation of the cellular and synaptic mechanisms underlying the loco-vestibulo-oculomotor interactions. The mouse introduces a greater complexity in gaze control as body movements, in contrast to frogs, are only partially transferred into head movements as recently demonstrated in humans. Importantly, our preliminary experiments have shown that in this higher vertebrate also, the spinal locomotor network exerts a central influence on the oculomotor system, consistent with an ubiquitous role in vertebrate gaze control. The mouse model will also allow the use of advanced tools not yet available in Xenopus, including transgenic vestibulo-deficient animals or specific neuroanatomical approaches with viral neuronal tracing.
2 partner laboratories are involved in this project; the complementarity of their scientific backgrounds and the combination of their respective technical skills will provide a strong and valuable asset for conducting this collaborative research project in close synergy. After a behavioral analysis of the locomotor and eye movement repertoires of both models in freely behaving vs head-fixed animals with 3D posturography and high-speed video cameras, we will use in vitro isolated or semi-intact preparations to identify the spino-extraocular pathways responsible for conveying the feed-forward command for gaze stabilization, as well as the synaptic and network mechanisms by which it influences the extraocular motor nuclei. In a further series of experiments we will explore the cellular and synaptic mechanisms underlying the interaction between the spinal efference copy and vestibular sensory inputs, since we have recently demonstrated in larval Xenopus that certain vestibular inputs are in fact gated out by the efference copy signals during locomotion.
In conclusion, with a multi-methodological integrative approach including in vivo behavioral video recording, neuroanatomy and a combination of functional imaging and cellular electrophysiological techniques our project is likely to provide a better mechanistic understanding of adaptive sensory-motor signaling and movement control in active vs passive conditions, as well as providing specific insights into pathological changes in gaze control following deficits in vestibular function.