Modulatory influence of stimulus parameters on optokinetic head-tracking response

Abstract

Optokinetic testing is a non-invasive technique, widely used for visual functional evaluation in rodents. The modulatory influence of optokinetic stimulus parameters such as contrast level and grating speed on head-tracking response in normal and retinal degenerate (RD) mice (rd10) and rats (S334ter-line-3) was evaluated using a computer-based testing apparatus. In normal (non-RD) mice and rats, specific stripe width and grating speed was found to evoke maximum optokinetic head-tracking response. In line-3 RD rats, the contrast sensitivity loss was slow and remained close to the baseline (normal control) level until very late in the disease, whereas, in rd10 mice the progression of the contrast sensitivity loss was more rapid. Observed differences between rd10 mice and line-3 RD rats in the progression of contrast sensitivity loss may not be directly related to the degree of photoreceptor loss. In young RD mice, the modulatory influence of stimulus parameters on optokinetic head-tracking response was similar to normal control animals. During later stages, slower grating speed was required to evoke the maximum optokinetic response. Grating speed had lesser apparent influence on the response properties of line-3 RD rats. Discrepancies between the two RD models in the modulatory influence of optokinetic stimulus parameters can be the manifestation of fundamental species differences and/or differences in the degeneration pattern. This study highlights the importance of careful selection of appropriate stimulus parameters for testing optokinetic head-tracking response in RD animals.

Figure 1

Progressive loss of contrast sensitivity in rd10 mice. The contrast sensitivity threshold for each animal was determined by changing the luminance level of the stripes by approximately 25 cd/m². The contrast sensitivity threshold was estimated based on whether any tracking behavior was observed. The sensitivity curve was constructed by plotting contrast vs age. The linear shape of the curve suggests consistent loss of contrast sensitivity in rd10 mice throughout the course of the disease progression.

Figure 2

Progressive changes in the contrast sensitivity in SS334ter-line-3 RD rats due to the progress of the RD disease. The contrast sensitivity threshold for each animal was determined by changing the luminance level of the stripes by approximately 25 cd/m². The contrast sensitivity threshold was estimated based on whether any tracking behavior was observed. The sensitivity was plotted using contrast vs age. In line-3 RD rats, the sensitivity remained close to the normal baseline (non-RD control) level during the initial phase of the disease. After 4 months of age, the contrast sensitivity plot showed a vertical deflection suggesting considerable loss of sensitivity at this age.

Figure 3

Progressive changes in the OHT response in rd10 mice evaluated by testing under varying grating speeds (mean±SE). Based on the level of head-tracking, the responses were scored on a scale of 0-4 (‘0’ = no response; ‘4’ = best response). RD mice were tested for head-tracking response once a month from 30 days to 6 months of age. (A) At younger ages (30-35 days), the optokinetic score was close to the normal control level; as the disease progressed, considerable loss of head-tracking score was observed. The grating speed that evoked the maximum head-tracking score changed during the progression of the disease.(B) Scatter plot demonstrating that in rd10 mice at early stages of degeneration (1 and 2 months of age), the maximum head-tracking score was observed at a grating speed that evoked the maximum response in normal control animals. As the disease further progressed (3, 4, and 5 months of age), maximum head-tracking score was apparent at a slower grating speed. The interaction between age and grating speed in determining the maximum head-tracking score is found to be statistically significant (Two Factor ANOVA, P<0.05).

Figure 4

Progressive changes in optokinetic response in SS334ter-line-3 RD rats evaluated at varying grating speeds (mean±SE). Based on the level of the head-tracking, the responses were scored on a scale of 0-4 (‘0’ = no response; ‘4’ = best response). Rats were tested for head-tracking response once a month from 30 days to 6 months of age. (A) optokinetic score at different grating speed plotted for normal Copenhagen rats (filled diamond) and S334ter-line-3 RD rats at 2- 6 months of age. (B) In RD rats no significant pattern is apparent to demonstrate a positive interaction between age and grating speed in determining the maximum head-tracking score (Two Factor ANOVA, P>0.05).