Measuring vision using innate behaviours in mice with intact and impaired retina function

Abstract

Measuring vision in rodents is a critical step for understanding vision, improving models of human disease, and developing therapies. Established behavioural tests for perceptual vision, such as the visual water task, rely on learning. The learning process, while effective for sighted animals, can be laborious and stressful in animals with impaired vision, requiring long periods of training. Current tests that that do not require training are based on sub-conscious, reflex responses (e.g. optokinetic nystagmus) that don't require involvement of visual cortex and higher order thalamic nuclei. A potential alternative for measuring vision relies on using visually guided innate defensive responses, such as escape or freeze, that involve cortical and thalamic circuits. In this study we address this possibility in mice with intact and degenerate retinas. We first develop automatic methods to detect behavioural responses based on high dimensional tracking and changepoint detection of behavioural time series. Using those methods, we show that visually guided innate responses can be elicited using parametisable stimuli, and applied to describing the limits of visual acuity in healthy animals and discriminating degrees of visual dysfunction in mouse models of retinal degeneration.

HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice

“…While we did not detect changes in ERGwave amplitudes in rd1 TN-XL mice treated at such late stages of degeneration, a modest improvement of ERG recordings was detected in rd10 mice following the treatment. Notably, despite ERG amplitudes remaining lower than in wild-type mice, the significant improvement in visually-driven behavior suggests that the potential benefits for the daily tasks of RP patients may be achievable even at the late stages of the disease [51]. It is very challenging to assess the effectiveness of vision therapy, even in patients.…”

A high dimensional quantification of mouse defensive behaviours reveals enhanced diversity and stimulus specificity

“…Among visual stimuli we selected a bright flash and a looming object. We have previously shown that these two stimuli evoke distinct and opposite behavioural responses, with the former inducing an increase in locomotor activity while the latter abolishes locomotion by inducing freezing behaviour [7].…”

“…This increase in specificity was particularly remarkable when comparing behavioural responses to a loud sound and a visual looming. It has been previously shown that both stimuli induce escape to a shelter or freeze when the shelter is not present [7,36]. As a result the responses to these stimuli have been considered equivalent and no attempts have been made to differentiate them.…”

“…Mice are innately able to respond to changes in their sensory landscape by producing sequences of actions aimed at maximizing their welfare and chances for survival. Such spontaneous behaviors as exploration [1,2], hunting [3,4], and escape and freeze [5][6][7][8], while heterogeneous, share the key property that they can be reproducibly elicited in the lab by controlled sensory stimulation. The ability of sensory stimuli to evoke a reproducible behavioural response in these paradigms makes them an important experimental tool to understand how inputs are encoded and interpreted in the brain, and appropriate actions selected [5,[8][9][10].…”

“…Instinctive defensive behaviours, such as escape or freeze have been defined on the basis of a clear phenotype -a sudden change in locomotion state. Thus in the last few years it has been shown that speed, size, luminance and contrast of a looming object have different and predictable effects on locomotion [5][6][7][8]. Nevertheless, mice do more than run, and a variety of other body movements as well as changes in body orientation and posture could, at least in principle, contribute to defensive behaviours.…”