XB-ART-57347J Neurol September 11, 2020;
Acute consequences of a unilateral VIIIth nerve transection on vestibulo-ocular and optokinetic reflexes in Xenopus laevis tadpoles.
Loss of peripheral vestibular function provokes severe impairments of gaze and posture stabilization in humans and animals. However, relatively little is known about the extent of the instantaneous deficits. This is mostly due to the fact that in humans a spontaneous loss often goes unnoticed initially and targeted lesions in animals are performed under deep anesthesia, which prevents immediate evaluation of behavioral deficits. Here, we use isolated preparations of Xenopus laevis tadpoles with functionally intact vestibulo-ocular (VOR) and optokinetic reflexes (OKR) to evaluate the acute consequences of unilateral VIIIth nerve sections. Such in vitro preparations allow lesions to be performed in the absence of anesthetics with the advantage to instantly evaluate behavioral deficits. Eye movements, evoked by horizontal sinusoidal head/table rotation in darkness and in light, became reduced by 30% immediately after the lesion and were diminished by 50% at 1.5 h postlesion. In contrast, the sinusoidal horizontal OKR, evoked by large-field visual scene motion, remained unaltered instantaneously but was reduced by more than 50% from 1.5 h postlesion onwards. The further impairment of the VOR beyond the instantaneous effect, along with the delayed decrease of OKR performance, suggests that the immediate impact of the sensory loss is superseded by secondary consequences. These potentially involve homeostatic neuronal plasticity among shared VOR-OKR neuronal elements that are triggered by the ongoing asymmetric activity. Provided that this assumption is correct, a rehabilitative reduction of the vestibular asymmetry might restrict the extent of the secondary detrimental effect evoked by the principal peripheral impairment.
PubMed ID: 32915311
Article link: J Neurol
Disease Ontology terms: vestibular nystagmus
Phenotypes: Xla wt + nerve section (Fig. 2.)
Article Images: [+] show captions
|Fig. 1 Experimental paradigm for evaluating acute consequences of a unilateral VIIIth nerve section on eye movements. a Isolated head preparation of a stage 55 Xenopus laevis tadpole with functional eyes, eye muscles, inner ears and neuronal circuits for ocular motor behavior; the inset on the right illustrates afferent innervation patterns of vestibular endorgans after tracer placement (Tetramethylrhodamine) into the vestibular nuclei. b Schematic of the vestibular hair cell—hindbrain vestibular nucleus (VN) connection depicting the VIIIth nerve, ganglion of Scarpa (G) and site of the postganglionic nerve section (lesion). c–e Schematics illustrating the three experimental paradigms used to evaluate the impact of the unilateral lesion: vestibulo-ocular reflex in darkness (VOR in darkness; c), in light (VOR in light; d) and optokinetic reflex (OKR; e). f Flow chart illustrating the temporal sequence of prelesional control recordings, nerve transection, and postlesional recordings of visuo-vestibular motion-evoked eye movements. AC, PC, HC anterior, posterior vertical, horizontal semicircular canal, HB hindbrain, Lag lagena, OC otic capsule, Sac saccule, Ut utricle. Scale bars in a are 2 mm and 50 µm, respectively|
|Fig. 2 Spontaneous and visuo-vestibular motion-evoked eye movements. a, b Infrared images (a) and static eye position of the left (LE) and right (RE) eye (b) before (upper image in a, black trace in b) and immediately after (0 h) transection of the right VIIIth nerve (lower image in a; magenta trace in b); dashed white lines in a indicate the major axis of the oval-shaped eyes, used to measure eye position and evoked motion. c Dot and whisker plot of the absolute eye position relative to the longitudinal body axis (left) and following subtraction of the prelesional eye position (right) in controls, immediately (0 h, magenta) and 1.5 h after transection of the right VIIIth nerve (cyan) in darkness. d-f Examples of movements of the left and right eye during four consecutive cycles of horizontal sinusoidal rotation of the head/table (0.5 Hz; ± 31.4°/s) in darkness (VOR in darkness; d), in light (VOR in light; e), and of horizontal sinusoidal motion (0.2 Hz; ± 12.6°/s) of a vertical black and white striped pattern (OKR; f) before (black traces) and immediately after (0 h) transection of the right VIIIth nerve (magenta traces); dashed sinusoids represent stimulus position profiles (Spos); arrowheads indicate eye movements evoked by head/table motion towards the intact (single arrowhead) and ipsilesional (two arrowheads) side; dotted orange line in d indicates the gradual shift in eye position towards the ipsilesional side with each rotation cycle. g Qualitative categorization of eye movements evoked by vestibular motion stimulation labeled as “successful”, “unsuccessful”, “fast phases” and “other”; dashed sinusoids represent the stimulus position (± 10°) profiles of the head/table motion cycle at 0.5 Hz. h Conjugation correlation plots of the position of the left and right eye during horizontal sinusoidal head/table rotation (VOR in darkness) before (black) and 1.5 h (cyan) after transection of the right VIIIth nerve; note that the position of both eyes is closely correlated indicating strict conjugation during the horizontal angular VOR before and after the lesion|
|Fig. 3 Immediate effects of a unilateral VIIIth nerve section on eye movement dynamics. a, b Relative proportion of “successful” VOR responses before (black), immediately (0 h, magenta) and 1.5 h postlesion (cyan) during sinusoidal rotation in darkness (a) and in light (b). c–e Averages of “successful” VOR responses in darkness (c), in light (d) and OKR responses (e) over a single sinusoidal stimulus motion cycle; averages are the mean of the responses from all preparations (n = 6), respectively; dashed sinusoids represent the stimulus position profile (Spos); arrowheads indicate eye movements evoked by head/table motion towards the intact (single arrowhead) and ipsilesional (two arrowheads) side, respectively. f–h Response gains (eye motion / stimulus motion) before, at 0 h and 1.5 h after the lesion for the VOR in darkness (f), in light (g) and the OKR (h). i–j Representative example traces of sinusoidal VOR eye movements over the first half cycle during head/table motion in darkness (i) and in light (j) directed towards the intact (left) and ipsilesional side (right) before (black traces) and immediately after the VIIIth nerve section (0 h, magenta traces); thin and thick lines represent individual and average responses, respectively. *p < 0.05; **p < 0.01; Dunn’s multiple comparisons test with respect to control values|
|Supplementary Fig. 1 Visuo-vestibular motion-evoked eye movements before and after a section of the VIIIth nerve. a-o Average responses (color-coded solid lines) ± SD (color-coded areas) over a single cycle of sinusoidal head/table motion in darkness (VOR in darkness), in light (VOR in light) and visual pattern motion (OKR) separately before the lesion (a-c), immediately after (0 hours; d-f), at 1.5 hours (g-i), 3 hours (j-l) and 4.5 hours postlesion (m-o) from all recorded preparations (n = 6), respectively; dashed sinusoids represent stimulus position profiles (Spos); note that the stimulus frequency and peak velocity for head/table motion is 0.5 Hz and 31.4°/s and for the visual pattern motion 0.2 Hz and 12.6°/s. p-r Overlay of average responses over single motion cycles shown in a-o from all time points (SDs were omitted) (EPS 9691 kb)|
|Supplementary Fig. 2 Proportional distribution and performance of motion-evoked eye movements before and after a section of the VIIIth nerve. a, b Relative proportions of the categories “successful”, “unsuccessful”, “fast phases” and “other” during head/table motion in darkness (VOR in darkness, a) and in light (VOR in light, b) before the lesion, immediately after (0 hours) and at 1.5 hours, 3 hours and 4.5 hours postlesion. c-e Progression of the response gain (eye motion / stimulus motion) before the lesion, immediately after (0 hours) and at 1.5 hours, 3 hours and 4.5 hours postlesion for the VOR in darkness (c), in light (d) and OKR (e); the time points in all plots are color-coded and specified in the right upper corner of a (EPS 755 kb)|