The vertebrate oculomotor integrator is responsible for stabilizing gaze at all eye positions by driving the extraocular motor nuclei with a steady rate of neural activity proportional to eye position. Disorders of this system can manifest as nystagmus. The integrator performs stability by maintaining a precisely tuned level of neural feedback. This level of feedback can be experimentally manipulated- the integrator has been shown to exhibit short-term plasticity in response to visual-vestibular conflict in humans. In the goldfish, a leaky or unstable neural integrator can be induced using visual feedback alone, by adjusting the velocity of an optokinetic stimulus in real-time as a function of horizontal eye position. The principal aim of the present study is to extend this methodology to humans. The preliminary data herein support the hypothesis that human oculomotor dynamics are manipulated by purely visual feedback. By measuring eye position with infrared eye-tracking technology and controlling the horizontal velocity of a computer-driven optokinetic stimulus, we have been able to elicit leakiness and instability in a small sample of normal human subjects. The current proposal aims to extend these findings and to broadly characterize this phenomenon in humans. The first set of experiments will compare several different optokinetic training paradigms for efficacy in producing the observed plasticity. In doing so, the time course of the effect and of recovery will be elucidated. Subsequent experiments will assess the repeatability of the effect and determine the dependence of recovery on stable visual feedback. Finally, we will make finer adjustments to the real-time visual feedback parameters in an attempt to mold integrator dynamics in a more detailed fashion than simply inducing leak or instability. The purpose of this line of research is 2-fold. Clinically, it is hoped that the principles revealed in this study can be adapted to alter neural integrator performance in patients with nystagmus. The gaze-evoked and pendular subtypes of nystagmus may be most tractable initially, since these forms have the most reliable relationship between eye position and drift velocity. Mechanistically, the human-relevance of goldfish integrator research has been recently supported by comparing high-resolution eye-movement measurements in the 2 species. These measurements reveal a high degree of quantitative similarity between their oculomotor systems, which is surprising in light of the vast differences between their visual systems. Repeating the goldfish plasticity experiments in humans will help in assessing the general relevance of ongoing vertebrate research aimed at revealing the cellular and network mechanisms of neural integration. ? ?
| Nickell, Stephan; Park, Paul S-H; Baumeister, Wolfgang et al. (2007) Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography. J Cell Biol 177:917-25 |
