Burgess, CP; (2016) Measuring correlates of perceptual decisions in mouse visual cortex. Doctoral thesis , UCL (University College London).

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Abstract

The activity of sensory cortex is determined not only by afferent sensory stimuli, but also by behavioural context factors such as movement, anticipation, attention, and reward. To investigate such factors, I developed a visual psychophysical task in head-fixed mice and combined it with two-photon calcium imaging to measure activity in primary visual cortex (V1). I trained mice to report the position of a grating by turning a wheel with their forepaws. I found that a crucial element in helping mice learn the task was enabling them to control the position of the stimulus: the grating would initially appear to their left or to their right, and their wheel turns would translate it. They were rewarded for bringing it to the centre. Mice typically learned the task in 2-3 weeks, producing high-quality psychometric functions of stimulus contrast, with 75% accuracy at contrasts as low as 8%. In the same mice, I injected a virus in V1 to express GCaMP6, so I could perform two-photon calcium imaging of neural populations while the mice performed the task. Calcium imaging in V1 revealed strong responses evoked by contralateral stimuli, modulated by stimulus contrast. I obtained measures of contrast sensitivity from population responses and found them to be higher than the corresponding psychophysical measures. I did not find significant correlations between perceptual decisions and stimulus-independent V1 activity. I also observed small but significant increases in calcium activity during pre-stimulus periods and the amplitude of this activity was predictive of subsequent psychophysical performance on those trials. Finally, I discovered that the basic task was adaptable and the stimulus control principle was generalizable. I demonstrate this by presenting multiple variants of the task including one using auditory stimuli and another probing the effects of dopamine stimulation.

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