319 The Mouse Model of Myopia
several times larger. Schmucker and Schaeffel50 elicited optomotor responses in mice by drifting 0.03 cyc/deg square wave gratings when mice were wearing trial lenses. Significant responses were found with +10 D of imposed defocus. In summary, at least for lower spatial frequencies, the depth of field of the mouse would exceed ±10 D.
Behavioral measurement of grating acuity and contrast sensitivity in the mouse
There were several approaches to measuring spatial visual performance in mice behaviorally. These approaches can be divided into two principles, testing forced choice behavior in a swimming task, the “Visual Water Task, VWT”51,52 or measuring the optomotor response to drifting gratings that are either presented as printed on paper and attached to the inner wall of a rotating drum, or more sophisticatedly, presented on computer monitors that are arranged in a square (the “virtual optomotor system, VOS”) that permitted better control of the stimulus variables.53–57 The first approach measures visual acuity for stationary targets, and the second for moving targets. Processing of the two stimulations involves different brain areas. While acuity for stationary targets is largely determined by geniculo-cor- tical processing, moving targets are processed in the subcortical accessory optic system.55 Prusky and Douglas58 have shown that ablation of the cortex did not change the cut-off spatial frequency measured with the visual water task (VWT) and the virtual optomotor system (VOS), but the contrast sensitivity functions were changed. Contrast sensitivity was increased in the VOS but the range of high contrast sensitivity was found at lower spatial frequencies (contrast sensitivity of about 20 at 0.05 cyc/deg with the VOS, but only about two with the VWT). Another interesting aspect observed in the VOS was that tracking occurred only in the temporal-to- nasal direction for each eye, similar to the condition in infants (e.g. Ref. 59). This means that, depending on the direction of motion of the stripes, each eye can be independently tested.55
Different body movements, elicited by the drifting gratings, can be studied: head tracking,53,60 optokinetic nystagmus of the eye,61,62 or whole body optomotor responses.14,27
It could be expected from the very bright retinal images of the mouse (see above — schematic eye data) that mice also have good spatial vision at low ambient illuminances. However, optomotor experiments in an
320 F. Schaeffel
Figure 8. Automated optomotor drum. The mouse is placed in a small inner perspex drum in the center of a larger drum, which is covered inside with the square wave stripe pattern (black arrow). The large drum is mechanically rotated by a DC motor. Both the center of mass of the mouse and the angular orientation of its body axis are automatically tracked by a video system (black arrow: small surveillance firewire camera that images the mouse, see also laptop screen). The net angular movement is statistically evaluated and compared to the stripe pattern’s direction of movement.14
automated optomotor drum suggest that this is not the case. Individual mice were placed in a small perspex drum in the center of a larger drum that was rotated with vertical square wave patterns of adjustable fundamental spatial frequency (Fig. 8).
Their movements were recorded from above by a little surveillance video camera. Movement analysis was fully automated. Both the angular movement of the center of mass of the mouse and angular changes in the orientation of the body axis were tracked by image processing
321 The Mouse Model of Myopia
software and automatically statistically analyzed. Even though the mice often ignored the visual stimuli when they cleaned themselves, the objective video tracking procedure produced statistically meaningful results. An advantage of the procedure was that the mice experienced no further behavioral restriction, causing little stress. The disadvantages are that the “whole body optomotor response” is less reliable than the eye61,62 or head63 optomotor response, and that the data is therefore more noisy.
The automated version of the “whole body optomotor analysis”14 provided some new results: Grating acuity reached its limit at about 0.4 to 0.5 cyc/deg, similar to other published optomotor experiments in which eye movements were evaluated. Grating acuity declined continuously when the illuminance (or luminance) was reduced: The “relative responses” were 100% at 400 lux (about 30 cd/m²), 76% at 40 lux (about
0.1cd/m²), and 46% at 4 lux (about 0.005 cd/m²). A similar decline in visual acuity with decreasing illuminances was also described by Abdeljalil et al.63 Mutant mice lacking either rods or cones, or both, showed reduced visual acuity in cone-only models (0.10 cyc/deg in Rho –/– and 0.20 cyc/deg in CNGB1–/– compared to 0.30 cyc/deg in C57BL/6 wild-type mice). The “all-rod-mouse” (CNGA3 –/–) performed similarly in the optomotor test as the wild-type, both under photopic and scotopic conditions. This observation suggests that the rod system is not saturated, even at illuminances of 400 lux (about 30 cd/m²). It should also be kept in mind that rods represent about 95% of the photoreceptors in most vertebrates,64 including the mouse. Since the remaining 5% of cones are not clustered in a fovea but rather more evenly distributed across the retina, they may not reach a sampling density necessary for good spatial vision. In mice without any functional photoreceptors (CNGA3 –/– Rho –/–), no optomotor response could be elicited, suggesting that the light sensitive, melanopsin-containing ganglion cells do not contribute to spatial vision.
In summary, the considerable number of behavioral studies have provided surprisingly consistent results: The highest contrast sensitivity of BL57J/6 mice is about 20 (equivalent to a threshold contrast of 5%) or even better (up to 10061), and is reached at high illuminances between 30 cd/m² 14 and 63 cd/m² 56 at spatial frequencies of between 0.1 and
0.2cyc/deg. The highest detected spatial frequency (denoted as “grating acuity”) is around 0.5 cyc/deg.