Unrestrained and hedonically motivated mouse psychophysics compatible with wireless optogenetic modulation.

BACKGROUND: Visual neuroscience research has adopted the mouse as one of its primary animal models. Collection of perceptually driven behavior in these mice often involves head fixation to present the visual stimulus under controlled conditions and water restriction to motivate responses. However, both head fixation and water restriction can induce physiological stress. NEW METHOD: Here, we adapted a popular open-source two-alternative-forced-choice (2AFC) visual psychophysics apparatus to allow unrestrained mice to maintain consistent stimulus viewing position while performing trials for hedonic reward. The stereotyped head positioning further enabled wireless power transfer to implanted LEDs, permitting transcranial optogenetic manipulation of targeted interneuron subtypes in visual cortex during behavior. RESULTS: Unrestrained mice learned a 2AFC contrast detection task, and required an average of 22.4 days to reach criterion accuracy. Mice showed strong task engagement with hedonic reward, and produced high quality psychometric functions based on thousands of trials. COMPARISON WITH EXISTING METHODS: Task acquisition times and accuracy were comparable to published head-fixed paradigms. Cortical illumination modulated contrast detection in a manner consistent with previous findings. CONCLUSIONS: This approach provides a less stressful and experimentally accessible alternative to head-fixation, lowering technical barriers while preserving the precision required for visual psychophysics.