Semicircular Canal Influences on the Developmental Tuning of the Translational Vestibulo-Ocular Reflex

Abstract

Vestibulo-ocular reflexes (VORs) rely on neuronal computations that transform vestibular sensory signals into spatio-temporally appropriate extraocular motor commands. The motoneuronal discharge for contractions of the superior oblique eye muscle during linear translation derives from a utricular epithelial sector that is spatially aligned with the pulling direction of this muscle. In Xenopus laevis, the alignment is gradually achieved during larval development and requires motion-related semicircular canal afferent activity. Here, we studied the origin of semicircular canal and utricular signals responsible for the establishment and maturation of the extraocular motor response vector. Experiments were conducted on semi-intact preparations of Xenopus tadpoles before and after unilateral transection of the VIIIth nerve and in preparations of animals in which semicircular canal formation was prevented on one side by the injection of hyaluronidase into the otic capsule prior to the establishment of the tubular structures. Unilateral VIIIth nerve sections revealed that the excitation underlying the contraction of the superior oblique eye muscle during horizontal linear acceleration and clockwise/counter-clockwise roll motion derives exclusively from the utricle and the posterior semicircular canal on the ipsilateral side. In contrast, the developmental constriction of the otolith response vector depends on signals from the posterior semicircular canal on the contralateral side. These latter signals suppress directionally incorrect components that derive from the utricular sector perpendicular to the superior oblique eye muscle. This directional tuning complies with a stabilization of spatially correct utricular inputs that are aligned with the extraocular motor target muscle. In addition, misaligned signals are concurrently suppressed by semicircular canal-related commissural pathways from the contralateral side and through local interneuronal inhibitory circuits within the ipsilateral vestibular nuclei.

Stabilization of Gaze during Early Xenopus Development by Swimming-Related Utricular Signals

“…First, bilateral injections of 0.5% MS-222 into the otic capsule, known to block vestibular afferent spike discharge [15] reversibly abolished both translational and eccentric rotational motion-evoked eye movements ( Figures 3A2,3 red traces, S4C). Second, bilateral semicircular canaldeficient stage 50 larvae were generated by hyaluronidase injections into both otic capsules at stage 44, as previously described in Xenopus [16][17][18]. As confirmation for the absence of bilateral semicircular canals and in compliance with prior studies [17,18], these animals completely lacked cyclic eye movements during rotation around a centered vertical axis ( Figure 3B1,C1).…”

“…Second, bilateral semicircular canaldeficient stage 50 larvae were generated by hyaluronidase injections into both otic capsules at stage 44, as previously described in Xenopus [16][17][18]. As confirmation for the absence of bilateral semicircular canals and in compliance with prior studies [17,18], these animals completely lacked cyclic eye movements during rotation around a centered vertical axis ( Figure 3B1,C1). However, lateral translation ( Figure 3B2,C2) as well as rotation around eccentric axes ( Figures 3B3,C3, S4E) evoked robust, compensatory eye movement.…”

“…The calibrated volume of 10 nl was pressure-injected (0.5 bar, 5 s) with a PICOSPRITZER III pressure injector (Intracel, UK). To prevent the developmental formation of semicircular canals on both sides, a previous established method was employed [16][17][18]. Accordingly, a calibrated volume (10 nl) of a hyaluronidase enzyme solution (0.5 mg/ml, Sigma-Aldrich, France), dissolved in artificial endolymph Ringer solution was injected into bilateral otic capsules of tadpoles at stage 44 (n = 5).…”

Locomotion-induced ocular motor behavior in larvalXenopusis developmentally tuned by visuo-vestibular reflexes

“…In fact, the spatial tuning of otolith signals in extraocular motoneurons depends on a co-activation of specific epithelial sectors of the utricle, spatially aligned with semicircular canals 25 . As supportive evidence for this assumption, the spatial tuning of utricular signals coincides with the appearance of the aVOR and is abolished in semicircular canaldeficient Xenopus larvae 25,41 . This spatial refinement of otolith signals by semicircular canal signals could also assist in the observed semicircular canal-dependent second maturation step of locomotion-induced eye movements.…”

Locomotion-induced ocular motor behavior in larval Xenopus is developmentally tuned by visuo-vestibular reflexes

“…In fact, the spatial tuning of otolith signals in extraocular motoneurons depends on a co-activation of speci c epithelial sectors of the utricle, spatially aligned with a particular semicircular canal 25 . As supportive evidence for this assumption, the spatial tuning of utricular signals coincides with the appearance of the aVOR and is abolished in semicircular canal-de cient Xenopus larvae 25,42 . This spatial re nement of otolith signals by semicircular canal signals could also assist in the observed semicircular canal-dependent second maturation step of locomotion-induced eye movements.…”