A Tactile Discrimination Task to Study Neuronal Dynamics in Freely-Moving Mice

Sensory discrimination tasks are valuable tools to study neuronal mechanisms of perception and learning. Most of the previously developed discrimination tasks for electrophysiological and imaging studies in rodents require the animals to be head-fixed. However, implementing neurophysiological recordings into more ethologically realistic settings with unrestrained animals has been challenging, especially for somatosensory studies. This study introduces a tactile discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, mice learn to discriminate between different aperture widths within days in order to forage for food rewards on a linear platform. We demonstrate that the task is whisker-dependent and that mice reliably discriminate aperture differences as small as 6 mm. The setup's versatility enables exploration into diverse behavioral aspects, including tactile discrimination thresholds, valence-dependent behavior, and cognitive flexibility following repeated task rule reversals. Rule learning was highly stereotypical, fast and reproducible across individual mice, with approximately 500 trials to attain expert level performance and approximately 1000 trials to relearn the first rule reversal. We further demonstrate that electrophysiological recordings and calcium imaging can be conducted in the same paradigm such that multiple behavioral read-outs (learning progression, whisker motion, whisker touch, reward licking) can be synchronized with respective electrophysiological and imaging data, providing a new versatile tool to elucidate neural mechanisms of cognition and sensory processing. ### Competing Interest Statement The authors have declared no competing interest.