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

R Storchi,J Wynne,R J Lucas,F P Martial,R Killick,C J Twining,J Rodgers,M Gracey,S Ryan,T F Cootes

doi:10.1038/s41598-019-46836-y

R Storchi, J Wynne + Show 8 more

Open Access

https://doi.org/10.1038/s41598-019-46836-y

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Journal: Scientific Reports	Publication Date: Jul 17, 2019
Citations: 19	License type: open-access

Affiliation: University of Manchester, Lancaster University

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.

Highlights

Rodents, and in particular mice, are increasingly applied to understanding the physiology and neural computations underlying vision
We considered two ways of using the tracking data to measure behavioural responses to a visual stimulus
Several potential barriers stood in the way of realising that potential at the start of this project: 1) the degree to which behaviourally salient stimuli used to evoke innate responses could be parameterised was unknown; in other words, to what extent a systematic variation of a stimulus parameter can induce measurable differences in behavioural responses? 2) reliable, automated and objective methods for measuring innate behavioural responses were not well defined; 3) the intrinsic variability of innate behaviours may make them too unreliable as an indicator of whether a mouse had detected a visual stimulus; 4) innate responses could quickly habituate; 5) the extent to which visually driven behaviours appear in animals with visual impairment was unexplored

Summary

Introduction

In particular mice, are increasingly applied to understanding the physiology and neural computations underlying vision. The aim of this work is to develop a rapid assay of visual stimulus detection, suitable for mice with intact and degenerate retinas, which doesn’t rely on training To meet these requirements we investigate the possibility of using innate behaviours instead of learned tasks. Several studies aimed at elucidating the circuits involved in controlling these behaviours revealed a substantial involvement of primary visual cortex[21,22] and first and higher order thalamic nuclei[23,24] as well as spatial memory[25] This indicates that these behaviours are not sub-conscious reflexes and instead rely on processing of higher order image forming pathways and integration with the limbic system. Innate responses are partially maintained in animals with impaired vision and can be used to discriminate different levels of vision loss

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