Homeostatic plasticity of eye movement performance in Xenopus tadpoles following prolonged visual image motion stimulation

Visual image motion-driven ocular motor behaviors such as the optokinetic reflex (OKR) provide sensory feedback for optimizing gaze stability during head/body motion. The performance of this visuo-motor reflex is subject to plastic alterations depending on requirements imposed by specific eco-physiological or developmental circumstances. While visuo-motor plasticity can be experimentally induced by various combinations of motion-related stimuli, the extent to which such evoked behavioral alterations contribute to the behavioral demands of an environment remains often obscure. Here, we used isolated preparations of Xenopus laevis tadpoles to assess the extent and ontogenetic dependency of visuo-motor plasticity during prolonged visual image motion. While a reliable attenuation of large OKR amplitudes can be induced already in young larvae, a robust response magnitude-dependent bidirectional plasticity is present only at older developmental stages. The possibility of older larvae to faithfully enhance small OKR amplitudes coincides with the developmental maturation of inferior olivary-Purkinje cell signal integration. This conclusion was supported by the loss of behavioral plasticity following transection of the climbing fiber pathway and by the immunohistochemical demonstration of a considerable volumetric extension of the Purkinje cell dendritic area between the two tested stages. The bidirectional behavioral alterations with different developmental onsets might functionally serve to standardize the motor output, comparable to the known differential adaptability of vestibulo-ocular reflexes in these animals. This homeostatic plasticity potentially equilibrates the working range of ocular motor behaviors during altered visuo-vestibular conditions or prolonged head/body motion to fine-tune resultant eye movements

Same same but different: plasticity of a 'conserved' reflex

Transformation of sensory percepts into motor output form a core element of how any animal interacts with their environment. While some such sensorimotor transformations can be very elaborate and depend on the lifestyle of a species, others serve basic functions and are ubiquitous across vertebrates. Among the latter ones are gaze-stabilizing reflexes, which serve to maintain stable vision during head motion through compensatory eye movements. Despite this conservation throughout evolution, these reflexive behaviors must remain plastic depending on context or past experience to maintain functionality after e.g. impairments of motor or sensory systems through compensation, or to changes in the environment through adaptation. In this thesis, I employ tadpoles of the frog Xenopus laevis to investigate how neuronal circuits contribute to either adaptive or compensatory plasticity on otherwise conserved gaze-stabilizing reflexes. My first study centers on the role of bilateral visual pathways in the development of the optokinetic reflex (OKR). In early embryos, I unilaterally remove the precursor of the eye, the optic vesicle. Tadpoles that develop under such monocular conditions display pathfinding errors of retinal ganglion cells at the optic chiasm. Tadpoles with near normal contralateral projections functionally compensate for the loss of one eye and show consistent responses to both leftward and rightward moving stimuli. In animals with an induced aberrant ipsilateral projection, compensation is increasingly impaired with more pathfinding errors. Combined, this study shows that binocular eyes are required for appropriate visual circuit formation, and that resulting anatomical aberrations impose limitations on compensatory plasticity. In my second study I focus on the role of the cerebellum in plasticity. Combinations of prolonged, repetitive stimulation with lesions of the cerebellum revealed adaptive plasticity of the OKR, where initially very variable OKR responses converge towards a homeostatic motor output by selective increase and decrease of response magnitude. The cerebellum is specifically associated only with response increases, and only starts to exert this influence well after initial OKR onset. This study therefore shows that multiple brain areas differentially contribute to plasticity of eye movements, leading to heterogenous appearance of different modes of plasticity throughout development. Combined, these studies contribute to the understanding of development and purpose of plasticity in Xenopus OKR. Multiple brain areas are involved with plasticity, and their formation depends on canonical, bilateral visual input. Once functional, plasticity mechanisms serve to maintain homeostasis of the OKR response in response to both adaptation and compensation

Influence of semicircular canal morphology on the VOR and swimming activity in larval amphibians: a comparative study in Xenopus and axolotl

Gaze stabilization and locomotion rely often on an accurate sensory detection of head movements by the vestibular system. A functional relationship between vestibular sensitivity, locomotor skills and semicircular canal morphology has been suspected in vertebrates as an adaptation to eco-physiological and species-specific needs, but has only partially and indirectly documented. However, evaluating the vestibulo-ocular reflexive activity and the locomotor efficiency simultaneously with the rotational sensor geometry remains absent from the literature. From such a perspective, this study attempted to provide a simultaneous quantification of the vestibulo-ocular response, the swimming efficiency and the canal morphology in the salamander axolotl and the frog Xenopus laevis, two amphibian species with comparable lifestyle and identical locomotor and vestibular systems at larval stages. Animals were studied at an equivalent developmental period: the late pre-metamorphic stage where the hindlimbs start to differentiate. Larval axolotl demonstrated an angular vestibulo-ocular reflex (aVOR) with a gain ~83% lower than Xenopus. Like in Xenopus at earlier stages, the aVOR gain increased in axolotl indicating a later functional onset. The morphological comparison of the semicircular canals of both species revealed that the horizontal canal in axolotl was thinner, less curved and less coplanar to the horizontal plane compared to Xenopus. Additionally, the ampulla of Xenopus was rounder and less elongated than in axolotl. All these parameters are critical for endolymph flow and consequently for the capacity of semicircular canals to perceive head motion. Interestingly, axolotl demonstrated a reduced swimming activity, more episodic than Xenopus, resulting in less frequent exposure to important head accelerations. Altogether, our results provide correlative evidences for a clear functional link between semicircular canal morphology, vestibular sensitivity, influencing aVOR performance, but also locomotor capacity in two comparable species, representative of anuran and salamander amphibians. This study, even preliminary, should open the pathway for further and more complete demonstrations of this functional relationship, that seems to be commonly shared during the evolution

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

Homeostatic plasticity of eye movement performance in Xenopus tadpoles following prolonged visual image motion stimulation.

Visual image motion-driven ocular motor behaviors such as the optokinetic reflex (OKR) provide sensory feedback for optimizing gaze stability during head/body motion. The performance of this visuo-motor reflex is subject to plastic alterations depending on requirements imposed by specific eco-physiological or developmental circumstances. While visuo-motor plasticity can be experimentally induced by various combinations of motion-related stimuli, the extent to which such evoked behavioral alterations contribute to the behavioral demands of an environment remains often obscure. Here, we used isolated preparations of Xenopus laevis tadpoles to assess the extent and ontogenetic dependency of visuo-motor plasticity during prolonged visual image motion. While a reliable attenuation of large OKR amplitudes can be induced already in young larvae, a robust response magnitude-dependent bidirectional plasticity is present only at older developmental stages. The possibility of older larvae to faithfully enhance small OKR amplitudes coincides with the developmental maturation of inferior olivary-Purkinje cell signal integration. This conclusion was supported by the loss of behavioral plasticity following transection of the climbing fiber pathway and by the immunohistochemical demonstration of a considerable volumetric extension of the Purkinje cell dendritic area between the two tested stages. The bidirectional behavioral alterations with different developmental onsets might functionally serve to standardize the motor output, comparable to the known differential adaptability of vestibulo-ocular reflexes in these animals. This homeostatic plasticity potentially equilibrates the working range of ocular motor behaviors during altered visuo-vestibular conditions or prolonged head/body motion to fine-tune resultant eye movements.</p

Acute consequences of a unilateral VIIIth nerve transection on vestibulo-ocular and optokinetic reflexes in Xenopus laevis tadpoles

AbstractLoss 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.</jats:p

Species-specific blood–brain barrier permeability in amphibians

Abstract Background The blood–brain barrier (BBB) is a semipermeable interface that prevents the non-selective transport into the central nervous system. It controls the delivery of macromolecules fueling the brain metabolism and the immunological surveillance. The BBB permeability is locally regulated depending on the physiological requirements, maintaining the tissue homeostasis and influencing pathological conditions. Given its relevance in vertebrate CNS, it is surprising that little is known about the BBB in Amphibians, some of which are capable of adult CNS regeneration. Results The BBB size threshold of the anuran Xenopus laevis (African clawed toad), as well as two urodele species, Ambystoma mexicanum (axolotl) and Pleurodeles waltl (Iberian ribbed newt), was evaluated under physiological conditions through the use of synthetic tracers. We detected important differences between the analyzed species. Xenopus exhibited a BBB with characteristics more similar to those observed in mammals, whereas the BBB of axolotl was found to be permeable to the 1 kDa tracer. The permeability of the 1 kDa tracer measured in Pleurodeles showed values in between axolotl and Xenopus vesseks. We confirmed that these differences are species-specific and not related to metamorphosis. In line with these results, the tight junction protein Claudin-5 was absent in axolotl, intermediate in Pleurodeles and showed full-coverage in Xenopus vessels. Interestingly, electron microscopy analysis and the retention pattern of the larger tracers (3 and 70 kDa) demonstrated that axolotl endothelial cells exhibit higher rates of macropinocytosis, a non-regulated type of transcellular transport. Conclusions Our study demonstrated that, under physiological conditions, the blood–brain barrier exhibited species-specific variations, including permeability threshold, blood vessel coverage, and macropinocytosis rate. Future studies are needed to test whether the higher permeability observed in salamanders could have metabolic and immunological consequences contributing to their remarkable regenerative capacity