A tactile discrimination task to study neuronal dynamics in freely-moving mice

Abstract

Sensory discrimination tasks are valuable tools to study neuronal mechanisms of perception and learning. Most 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. Here, we introduce a whisker-dependent discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, male mice learned to discriminate aperture widths within days while foraging on a linear platform. The setups 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. Electrophysiological recordings revealed distributed tactile processing across the thalamocortical system, with subsets of units encoding both movement- and stimulus-related features. Sensory encoding was strongly modulated by behavioral state, with neurons tuned to locomotion, whisking, whisker angle and phase, head angle, and spatial position. By enabling simultaneous extracellular recordings and calcium imaging within the same freely moving paradigm, this approach allows for precise synchronization of neural activity with multiple behavioral readouts. This paradigm provides a versatile tool to elucidate neural mechanisms of cognition and sensory processing in naturalistic conditions.