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. 2018 Jun 5;9:404.
doi: 10.3389/fneur.2018.00404. eCollection 2018.

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

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Free PMC article

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

Francisco Branoner et al. Front Neurol. .
Free PMC article

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.

Keywords: VOR; Xenopus laevis; extraocular motoneuron; eye muscle; otolith organ; utricle.

Figures

Figure 1
Figure 1
Arrangement of eye muscle pulling directions and semicircular canal planes. (A) Schematics depicting the spatial alignment of the three semicircular canals (left) and the six extraocular muscles (right) of the left inner ear and eye, respectively; note that color-coded antagonistic pairs of eye muscles are approximately aligned with individual semicircular canals. (B) Mean orientation of vertical semicircular canals and eye muscle pulling directions (± SEM) relative to the body length axis in tadpoles at developmental stage 46 and 55 (from n = 5 animals, respectively). (C) Exemplary orientations of semi-intact tadpole preparations either longitudinally on the linear sled (0°, middle) or in positions in which the SO eye muscle (magenta arrow) was either oriented parallel (left, 45°) or perpendicular (right, 315°) to the translational motion direction (double-headed black arrow). HC horizontal semicircular canal; AC, PC anterior, posterior vertical semicircular canal; IO, IR, inferior oblique, rectus muscle; LR, MR, lateral, medial rectus muscle; SO, SR, superior oblique, rectus muscle.
Figure 2
Figure 2
Spontaneous and motion-induced spike discharge of the SO nerve. (A–C) Multi-unit activity of the left SO nerve (color-coded traces in A2,B2,C2) in the absence of motion (A1, 2) and during four cycles of sinusoidal horizontal linear translation on a sled (Spos; black traces in B,C) at 0.5 Hz and 0.49 m/s2peak acceleration; preparations were positioned on the sled such that the SO muscle was oriented parallel (B1) or perpendicular (C1) to the translational motion direction; PSTHs (bin width: 50 ms) of spontaneous (A3) and averaged SO nerve firing rates over a single cycle (dashed sine waves) of sled motion (from n = 20–30 cycles), respectively (B3,C3); the dotted line in (A3) indicates the average resting rate and the arrow heads in (B3,C3) the phase-time of the minimal (red) and maximal (blue) discharge. (D) Mean ± SEM of averaged SO nerve discharge modulation (D1; n = 8 preparations) over a single cycle (dashed sine wave) during linear motion parallel (violet) and perpendicular (red) to the SO muscle pulling direction; bar plot (D2) of normalized SO nerve firing rate modulation during translation parallel (violet) and perpendicular (red) to the SO eye muscle pulling direction (n = 8); significance of difference between the normalized response rates during motion in the two directions is indicated (**p ≤ 0.01; Wilcoxon signed-rank test); polar plot (D3) depicting the directional distribution of SO nerve discharge modulation magnitudes across 360° of translational motion (gray area) and preferential (violet arrow) and approximately orthogonal response vectors (red arrow); the dotted orange circle in D3 indicates the average resting rate. SO, superior oblique; Spos, stimulus position of the sled.
Figure 3
Figure 3
Consequences of unilateral VIIIth nerve lesions on motion-induced SO nerve firing rate modulation. (A,B) Discharge modulation of bilateral SO nerves during four cycles of sinusoidal horizontal linear translation on a sled at 0.5 Hz and 0.49 m/s2peak acceleration (Spos; black traces) before (A1) and after transection of the right VIIIth nerve (B1); for maximal discharge modulation, preparations were positioned such that the left (A2,B2; blue traces) and right SO muscle (A3,B3; violet traces) were oriented parallel to the translation direction, respectively; note the complete loss of SO nerve spike activity on the ipsilesional (B3) and persistence of firing rate modulation on the contralesional side (B2). (C–F) PSTHs (bin width: 50 ms) of averaged firing rate modulation over a single cycle (dashed sine waves in C,D) of sled motion (from n = 20–30 cycles) and polar plot of modulation magnitudes across 360° of translational motion (E,F) of the contralateral SO nerve before (C,E) and after VIIIth nerve transection (D,F); data in (C–F) derive from the typical example depicted in (A,B); dotted orange circles in (E,F) indicate the respective resting discharge rates. (G) Bar plot of normalized SO motor nerve firing rate modulation during translation parallel (orange) and perpendicular (red) to the SO eye muscle pulling direction (n = 8) before and after VIIIth nerve transection. SO, superior oblique; Spos, stimulus position of the sled.
Figure 4
Figure 4
Morpho-physiological correlates of impaired angular VOR in unilateral semicircular canal-deficient Xenopus tadpoles. (A) Scheme depicting the injection of the hyaluronidase into the right otic capsule (OC, light red). (B1–B3) Overview (B1) of a horizontal section through the head of a stage 55 tadpole, which received a hyaluronidase injection into the right otic capsule at stage 44; higher-magnification of the boxed areas in (B1) of the left (B2) and right inner ear (B3), indicating that semicircular canals developed on the left but not on the right side (red * in B1, 3 indicate putative locations of AC and PC). (C–E) Schematics of positional orientations of the preparations to record the right (C,D) and left (E) SO nerve during vertical-axis rotation; positional arrangements allow selective rotational stimulation at 1 Hz and ± 60°/s peak velocity of the right PC—left AC (C,D) or left PC—right AC (E), without stimulation of the utricle. (F) Spike discharge modulation of the right SO nerve during five cycles of sinusoidal turntable rotation (Tpos; black trace in (F1)) and averaged firing rate (mean ± SEM; F2) over a single cycle (dashed sine wave in F2) in a control. (G,H) Spike discharge modulation of the right (G1) and left SO nerve (H1) during sinusoidal rotation [Tpos; black traces in (G1,H1)] in a preparation from a typical unilateral (right side) semicircular canal-deficient tadpole (red labeled inner ear); averaged firing rates (mean ± SEM; G2,H2) over a single cycle (dashed sine waves in G2,H2) show the loss of the excitatory (G2) or inhibitory response component (H2); the averaged firing rate modulation over a single cycle in (F2,G2,H2) was obtained from 20–30 cycles, respectively. AC, PC, anterior, posterior vertical semicircular canal; SO, superior oblique; Tpos, stimulus position of the turntable, C, caudal; R, rostral. Calibration bar represents 2 mm in (B1) and 0.5 mm in (B2,B3).
Figure 5
Figure 5
Impact of unilateral semicircular canal-deficiency on the developmental tuning of translational motion-evoked SO nerve responses. (A) Schematics depicting the presence of semicircular canals in the left and the absence thereof in the right inner ear in a stage 55 tadpole. (B,C) Spike discharge of the left (B) and right SO nerve (C) during four cycles of sinusoidal horizontal linear translation on a sled at 0.5 Hz and 0.49 m/s2peak acceleration (Spos; black trace) in a direction parallel (upper blue and magenta trace) and perpendicular to the SO eye muscle pulling direction (lower blue and magenta trace), respectively. (D,E) PSTH (bin width: 50 ms) of averaged firing rate modulation over a single cycle (dashed sine waves in D,E) of sled motion (from n = 20–30 cycles) of the left (D) and right SO nerve (E) during the two orthogonal translation directions. (F–H) polar plot of SO nerve discharge modulation magnitudes (F,G) and bar plot (H) of normalized firing rate modulation during translation along the two orthogonal directions of the left (blue) and right SO nerve (magenta); note the absence of directionally tuned responses of the SO nerve contralateral to the semicircular canal-deficient inner ear, indicated by the omni-directional vector plot (blue in F) and similar response magnitudes (blue bars in H) during translation parallel and perpendicular to the SO eye muscle pulling direction (n = 8), at variance with the corresponding responses of the SO nerve ipsilateral to the impaired inner ear (magenta vector plot in (G) and bar plot in (H); **p ≤ 0.01; Wilcoxon signed-rank test); red arrows in (G) indicate response components at spatial orientations, which became abolished during development. Dotted white circles in (F) and (G) indicate the SO nerve resting rates. n.s., not significant; SO, superior oblique; Spos, stimulus position of the sled.
Figure 6
Figure 6
Schematics depicting the hindbrain connectivity of vestibular endorgans and the SO eye muscle along with the developmental changes in utricular and semicircular canal contributions during the developmental tuning of the SO nerve response vector. At stage 46, SO nerve responses derive from the entire utricle (yellow labeling on the right), whereas at stage 55, SO nerve responses derive from a utricular sector that aligns with the PC on the same side; the spatial restriction of the response vector in the direction perpendicular to the SO muscle derives from the contralateral PC (red labeling on the left) and is potentially mediated by midline crossing inhibitory pathways. AC, PC, HC, anterior, posterior vertical, horizontal semicircular canal; IO, inferior oblique; IR, inferior rectus; LR, lateral rectus; MR, medial rectus; PCe, excitatory PC neuron; r1-8, rhombomere 1-8; SO, superior oblique; SR, superior rectus, PCcom, posterior canal commissural neuron; SOMot, superior oblique motoneuron.

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