Dietrich H and Straka H (2016), Prolonged vestibular stimulation induces homeos...

XB-ART-52079

Eur J Neurosci 2016 Jul 01;441:1787-96. doi: 10.1111/ejn.13269.

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Prolonged vestibular stimulation induces homeostatic plasticity of the vestibulo-ocular reflex in larval Xenopus laevis.

Dietrich H , Straka H .

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Vestibulo-ocular reflexes (VOR) stabilise retinal images during head/body motion in vertebrates by generating spatio-temporally precise extraocular motor commands for corrective eye movements. While VOR performance is generally robust with a relatively stable gain, cerebellar circuits are capable of adapting the underlying sensory-motor transformation. Here, we studied cerebellum-dependent VOR plasticity by recording head motion-induced lateral rectus and superior oblique extraocular motor discharge in semi-intact preparations of Xenopus laevis tadpoles. In the absence of visual feedback, prolonged sinusoidal rotation caused either an increase or decrease of the VOR gain depending on the motion stimulus amplitude. The observed changes in extraocular motor discharge gradually saturated after 20 min of constant rotation and returned to baseline in the absence of motion stimulation. Furthermore, plastic changes in lateral rectus and superior oblique motor commands were plane-specific for horizontal and vertical rotations, respectively, suggesting that alterations are restricted to principal VOR connections. Comparison of multi- and single-unit activity indicated that plasticity occurs in all recorded units of a given extraocular motor nucleus. Ablation of the cerebellum abolished motoneuronal gain changes and prevented the induction of plasticity, thus demonstrating that both acquisition and retention of this type of plasticity require an intact cerebellar circuitry. In conclusion, the plane-specific and stimulus intensity-dependent modification of the VOR gain through the feed-forward cerebellar circuitry represents a homeostatic plasticity that likely maintains an optimal working range for the underlying sensory-motor transformation.

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Species referenced: Xenopus laevis
GO keywords: reflex [+]

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	Figure 1. Extraocular motor discharge during motion stimulation in Xenopus. A, Photomicrograph depicting a semi-intact tadpole preparation with functionally intact bilateral otic capsules, central nervous system and eyes. Red dashed lines indicate rostro-caudal positions for forebrain and spinal cord removal. B, Eye muscles and innervating extraocular motor nerve branches, isolated for suction electrode recordings of the lateral rectus (LR) and superior oblique (SO) motor nerves. C, Schematic of the experimental setting depicting the semi-intact preparation as well as the activation of LR (green) and SO (magenta) motor nerves during horizontal and vertical rotational stimulation of the bilateral horizontal (HC, green) or the ipsilateral posterior (iPC, magenta) and contralateral anterior (cAC, magenta) semicircular canals respectively. D, Representative example of multi-unit LR (left) and SO (right) nerve spike discharge over three cycles of horizontal and vertical head rotation (0.5 Hz) at three different stimulus peak velocities. E,F, Dependency of peak amplitude (black curves) and phase (green and magenta curves respectively) of rotation-evoked cyclic multi-unit LR (left) and SO (right) motor nerve responses (±SEM; n = 10) on stimulus peak velocity (E) and frequency (F). abd, abducens nucleus; hor/ver vel, horizontal/vertical head velocity; ON, optic nerve; tro, trochlear nucleus; VN, vestibular nucleus. Image in B was modified from Lambert et al. (2008).
	Figure 2. Alterations of LR nerve discharge magnitudes following prolonged horizontal head rotation. A, Schematic depicting the experimental paradigm used for the induction of bidirectional plastic changes of the extraocular motor output. B, Time-dependent alterations of LR nerve peak firing rates (±SEM; n = 9) during prolonged sinusoidal rotation at 0.5 Hz with either high (±60°/s, blue) or low (±6°/s, red) stimulus peak velocities (conditioning stimulus amplitudes). C, Representative example of a multi-unit LR nerve discharge over three cycles of horizontal head rotation (Hvel, dashed green line) at the test stimulus intensity (0.5 Hz, ±30°/s peak velocity) before and after 10 and 20 min (colour-coded traces) of high-amplitude conditioning stimulation. D, Normalised LR nerve firing rate modulation (±SEM, shaded areas) at the test stimulus intensity averaged over a single cycle (n = 9) before and after different durations of prolonged high-amplitude conditioning stimulation (colour-coded curves). E, Dependency of the normalised peak firing rate of LR nerve test responses on the duration of high-amplitude conditioning stimulation (red symbols and line of exponential decay fit with a time constant of τ = 10.4 s) and after keeping the preparation stationary for 20 min. Black symbols depict unaltered peak firing rates during prolonged stimulation at the test stimulus (±SEM; n = 6). F,G, Representative example of a multi-unit LR nerve discharge over three cycles of horizontal head rotation (Hvel, dashed red line) at the test stimulus intensity (F) and respective normalised LR nerve test responses averaged over a single cycle (±SEM, shaded areas; n = 9) (G) before (black) and after 20 min of high (blue) and low (red) amplitude conditioning stimulation respectively. H, Box plots depicting peak firing rates of test responses (left) and individual differences in peak firing rates (right) before (black) and after 20 min of prolonged low (red) and high (blue) amplitude conditioning stimulation (n = 9). Boxes indicate median and lower and upper quartiles; bars represent minimum and maximum values and crosses outliers (left). Individual differences are plotted as open black circles; mean ± SD in red and blue respectively (right). I, LR test responses (0.5 Hz, ±30°/s) averaged over a single motion cycle (±SEM, shaded areas; n = 6) before (black) and after 20 min conditioning stimulation at a constant peak velocity but lower (0.1 Hz; light blue) or higher (1 Hz; magenta) stimulus frequency. Dashed lines in D,G,I indicate head motion stimulus velocity (Hvel). , P < 0.05; * P < 0.01.
	Figure 3. Alterations in discharge magnitudes of single LR motor units following prolonged horizontal head rotation. A–D, Representative examples of two isolated LR motor units (unit 1 and 2) during three cycles (0.5 Hz) of horizontal head rotation (Hvel; A) and overlays of the corresponding spike shapes before (black) and after 20 min of low- (red) and high-amplitude (blue) conditioning stimulation respectively (B). Firing rate modulation of unit 1 (C) and unit 2 (D) averaged over a single cycle at the test stimulus intensity (±30°/s peak velocity) before (black) and after 20 min of low (red) and high (blue) amplitude conditioning stimulation respectively. E, Averaged firing rate modulation of unit 2 over a single cycle at the same stimulus frequency (0.5 Hz), but different peak velocities (colour-coded). F, Box plots depicting peak firing rates of single unit test responses (left) and individual differences in peak firing rates (right) before (black) and after 20 min of prolonged low- (red) and high-amplitude (blue) conditioning stimulation (n = 11). Boxes indicate median and lower and upper quartiles; bars represent minimum and maximum values and crosses outliers. Individual differences are plotted as open black circles; mean ± SD in red and blue respectively (right). Dashed lines in C–E indicate head motion stimulus velocity (Hvel).
	Figure 4. Plane-specific alterations of the SO nerve discharge following prolonged horizontal head rotation. A, Representative example of a multi-unit SO nerve discharge over three cycles of horizontal head rotation (Hvel, dashed red line; pictogram) at the test stimulus intensity (0.5 Hz, ±30°/s peak velocity). B–E, Representative examples of a multi-unit SO nerve discharge over three cycles of vertical head rotation along the iPC-cAC plane (dashed red lines; pictogram) at the test stimulus intensity for vertical rotation (0.5 Hz, ±15°/s peak velocity; B,C) and firing rate modulation averaged over a single cycle (D,E; n = 6, respectively; ±SEM, shaded areas); recordings were obtained before (black) and after 20 min of conditioning stimulation at high (blue) and low (red) amplitude horizontal (B,D) and vertical (C,E) sinusoidal head rotation respectively; note alterations of SO nerve responses following vertical but not horizontal conditioning stimulation. F, Box plots depicting peak firing rates of SO nerve test responses (left) and individual differences in peak firing rates (right) before (black) and after 20 min of prolonged low (red) and high (blue) amplitude conditioning stimulation in the iPC-cAC plane (vertical rotation; n = 6). Boxes indicate median and lower and upper quartiles; bars represent minimum and maximum values. Individual differences are plotted as open black circles; mean ± SD in red and blue respectively (right). Dashed lines in D,E indicate head motion stimulus velocity (Hvel). hor/ver rot, horizontal/vertical head rotation.
	Figure 5. Cerebellar role in extraocular motor plasticity. A,B, Schematics depicting the three-neuronal vestibulo-ocular pathway and the cerebellar side loop, controlling the VOR output (A) and the site of surgical removal of the cerebellum in the semi-intact Xenopus preparation (B). C, Representative example of a multi-unit LR nerve discharge over three cycles of horizontal head rotation (Hvel, dashed red line) at the test stimulus intensity (0.5 Hz, ±30°/s peak velocity); recordings were obtained in the same preparation before (black), after 20 min of high-amplitude conditioning stimulation (blue), immediately after cerebellectomy (green), after 20 min of low-amplitude conditioning stimulation (light red) and 20 min after high-amplitude conditioning stimulation (light blue), both of the latter in the absence of the cerebellum. D,E, LR firing rate modulation averaged over a single cycle at the test stimulus intensity (n = 6; ±SEM, shaded areas) before (black) and after 20 min of high-amplitude conditioning stimulation immediately before (blue) and after cerebellectomy (green) (D) as well as after 20 min of low- (red) and high-amplitude (blue) conditioning stimulation in the absence of the cerebellum (E). Inset in D shows LR nerve resting rates before (black) and after (green) cerebellectomy (±SEM; n = 7). F, Box plots depicting peak firing rates of LR nerve test responses (n = 6) in the absence of the cerebellum before (black) and after 20 min of prolonged low (red) and high (blue) amplitude stimulation (left) and individual differences in peak firing rates before and after prolonged stimulation (right). Boxes indicate median and lower and upper quartiles; bars represent minimum and maximum values and crosses outliers. Individual differences are plotted as open black circles; mean ± SD in red and blue respectively (right). Dashed lines in D,E indicate head motion stimulus velocity (Hvel). 1°VN, 2°VN, first- and second-order vestibular neurons; CB, cerebellum; cAC, contralateral anterior canal; GC, granule cells; HC, horizontal canal; iPC, ipsilateral posterior canal; MN, extraocular motoneurons.