The opto-locomotor reflex as a tool to measure sensitivity to moving random dot patterns in mice (original) (raw)

We designed a method to quantify mice visual function by measuring reflexive opto-locomotor responses. Mice were placed on a Styrofoam ball at the center of a large dome on the inside of which we projected moving random dot patterns. Because we fixed the heads of the mice in space and the ball was floating on pressurized air, locomotion of the mice was translated to rotation of the ball, which we registered. Sudden onsets of rightward or leftward moving patterns caused the mice to reflexively change their running direction. We quantified the opto-locomotor responses to different pattern speeds, luminance contrasts, and dot sizes. We show that the method is fast and reliable and the magnitude of the reflex is stable within sessions. We conclude that this opto-locomotor reflex method is suitable to quantify visual function in mice. In recent years, mice have become an important animal model for studies on visual processing. Although mice rely much less on vision than primates, their visual system largely resembles that of higher mammals 1-4. Moreover, mice offer unique opportunities to study the functional circuitry of vision. For example, through the invention of genetically encoded calcium current and voltage indicators it is possible to record in parallel the activity of hundreds of neurons in cortex in the behaving mouse 5-10. The activity of large groups of neurons can be altered by applying optogenetics 11-14 or activated by designer drugs 15,16. These neurophysiological techniques offer the opportunity to directly relate neuronal function in retina and visual cortex to visually driven behaviour 2,17-20. For this purpose, suitable tests of visual function are needed. Over the years many behavioural tests for mouse visual function have been developed 21-23. Visual function in mice is traditionally tested with simple behavioural paradigms based on reflexes, such as the eye blink reflex, the pupil light response 21,24 , light-dark transition test 25 and optokinetic reflexive responses of the eye or the head to large moving patterns 26-29. These reflexes are thought to rely on the retino-tectal pathway, which is strongly developed in the mouse 30-32. Higher perceptual facilities (pattern, depth, orientation) are thought to rely more on retino-cortical pathways. Examples of tests that probe these are the visual cliff test 33 and modified Morris water maze tests 34-37. Many recent studies of mouse visual perception rely on fixating the head in space. This has the advantage of increased control over the visual stimulation and it provides the stability that is typically required in neural techniques such as two-photon calcium imaging 20,38,39 and single unit or patch-clamp recording 40,41. Perceptual tasks that head-fixed mice perform concurrently with these neurophysiological assays typically involve licking responses or lever presses to visual stimuli according to specific, trained rules of varying complexity 21,40,42-47. The purpose of this study is to test a method we developed that leverages the opto-locomotor reflex (OLR) in a head-fixed paradigm. This reflex effectively stabilises whole-scene motion by cancelling it with a body orienting movement of the same magnitude 46-50. In this study, we fixed mice with their heads over the center of a spherical, 2D treadmill. All mice spontaneously started running forward. The treadmill was located at the center of a 112 cm dome on the inside of which we projected moving random dot patterns. The presentation of rightward or leftward moving patterns caused the mice to reflexively change their running direction. We quantified the