Compensatory eye movements in mice

This thesis will address the generation of compensatory eye movements in naturally mutated or genetically modified mice. The reason for generating compensatory eye movements is solely related to the requirements for good vision. In a subject moving through its environment the projection of visual surround would slip across the retina and retinal slip of more than only a few degrees per second would cause blurring of the projected image and reduce visual acuity (Westheimer and McKee, 1975). Compensatory eye movements are therefore generated to assure that visual projections on the retina remain at approximately the same retinal coordinates, thereby preserving a stable image despite perturbations due to self-generated or imposed movement of the head. Because of its relative simplicity the oculomotor system, which encompasses the entire transformation from sensory input to the generation of compensatory eye movements, has served as a particularly useful model for physiologists who try to understand how the brain controls movement. The repertoire of possible movements in the oculomotor system is limited to those of the eyeball in its socket, which constitutes a single joint on which three pairs of extra-ocular muscles exert their force. Each pair of muscles affects movement around one of three orthogonal rotational axes and due to a fairly constant mechanical load on the eye muscles no stretch reflex is needed. This relative simplicity of the oculomotor system and the fact that both behavioral output and sensory input can be readily measured makes it amenable to detailed quantitative analysi

The dynamic characteristics of the mouse horizontal vestibulo-ocular and optokinetic response

In the present study the optokinetic reflex, vestibulo-ocular reflex and their interaction were investigated in the mouse, using a modified subconjunctival search coil technique. Gain of the ocular response to sinusoidal optokinetic stimulation was relatively constant for peak velocities lower than 8°/s, ranging from 0.7 to 0.8. Gain decreased proportionally to velocity for faster stimuli. The vestibulo-ocular reflex acted to produce a sinusoidal compensatory eye movement in response to sinusoidal stimuli. The phase of the eye movement with respect to head movement advanced as stimulus frequency decreased, the familiar signature of the torsion pendulum behavior of the semicircular canals. The first-order time constant of the vestibulo-ocular reflex, as measured from the eye velocity decay after a vestibular velocity step, was 660 ms. The response of the vestibulo-ocular reflex changed with stimulus amplitude, having a higher gain and smaller phase lead when stimulus amplitude was increased. As a result of this nonlinear behavior, reflex gain correlated strongly with stimulus acceleration over the 0.1-1.6 Hz frequency range. When whole body rotation was performed in the light the optokinetic and vestibular system combined to generate nearly constant response gain (approximately 0.8) and phase (approximately 0°) over the tested frequency range of 0.1-1.6 Hz. We conclude that the compensatory eye movements of the mouse are similar to those found in other afoveate mammals, but there are also significant differences, namely shorter apparent time constants of the angular VOR and stronger nonlinearities

Oculomotor plasticity during vestibular compensation does not depend on cerebellar LTD

Vestibular paradigms are widely used for investigating mechanisms underlying cerebellar motor learning. These include adaptation of the vestibuloocular reflex (VOR) after visual-vestibular mismatch training and vestibular compensation after unilateral damage to the vestibular apparatus. To date, various studies have shown that VOR adaptation may be supported by long-term depression (LTD) at the parallel fiber to Purkinje cell synapse. Yet it is unknown to what extent vestibular compensation may depend on this cellular process. Here we investigated adaptive gain changes in the VOR and optokinetic reflex during vestibular compensation in transgenic mice in which LTD is specifically blocked in Purkinje cells via expression of a peptide inhibitor of protein kinase C (L7-PKCi mutants). The results demonstrate that neither the strength nor the time course of vestibular compensation are affected by the absence of LTD. In contrast, analysis of vestibular compensation in spontaneous mutants that lack a functional olivocerebellar circuit (lurchers) shows that this form of motor learning is severely impaired. We conclude that oculomotor plasticity during vestibular compensation depends critically on intact cerebellar circuitry but not on the occurrence of cerebellar LTD. Copyrigh