Patients suffering from Alzheimer's disease (AD) have massive impairments in learning and memory, but also deficits in the processing of sensory information. Different sensory modalities can be affected, including information processing in the visual system. In the present study we tested whether transgenic APP23xPS45 mice, suffering from the central symptoms of AD, like learning and memory deficits, show also impairments in processing visual information. For this purpose, we tested 3 and 8–10 month-old mice. First, we assessed the optomotor behaviour by exploring the spontaneous response of mutant and wild type (wt) mice to drifting gratings presented on four computer monitors arranged around the test arena (Prusky et al., 2005). Both wt and transgenic animals at both ages tested had reliable optomotor responses, indicating that the mice could see the gratings presented on the monitors. Next, we tested for impairments in processing visual information in a new visual pattern discrimination task (modified from Wong et al., 2007). In a water maze, the mice were trained to distinguish between visual cues presented on two computer monitors. The correct cue was associated with a submerged platform positioned in front of one monitor (correct choice). As visual cues we presented gratings with the same spatial and temporal frequencies than that were also used for inducing optomotor responses. Both wt and AD mice of both ages discriminated significantly above chance level gratings separated by 45°. After reducing the angle between the two gratings to 22.5°, wt mice at an age of 8–10 month still reached a level of 67% correct choices, whereas the performance of the mutant mice did not exceed chance level. We verified that the mice were capable of completing the task by determining the proportion of trials in which the mice reached either the platform located in front of the correct cue or the position of the platform in front of the wrong cue. Our results demonstrate that APP23xPS45 mutant mice represent a powerful model system for studying age-dependent impairments in visual information processing related to AD. An in vivo two-photon imaging analysis of visually-evoked signals in cortical neurons in this mouse model of AD is in progress.

Prusky, G.T. et al., Invest Ophthalmol Vis Sci 45, 4611-6 (2004). Wong, A.A. and Brown, R.E., Neurobiol Aging 28, 1577-93 (2007).