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

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