Brain-wide Hierarchical Encoding of Working Memory

The brain is efficient to categorize continuous sensory inputs into discrete perceptions to aid efficient action. The brain-wide neural mechanism underlying this sensory-to-categorical transformation remains elusive. Here we recorded brain-wide neuronal activity by Neuropixels probes in mice performing a two-alternative forced choice (2AFC) odor categorization task, using different combinations of odor mixtures. Mixtures of two pure odors were delivered at different ratios, and the left or right lick decision after a delay period should be based on the category defined by the dominant odor. Mice showed lower performance in the trials with smaller difference in odor concentration. We recorded more than 30,000 neurons from over 100 regions in 14 mice (Figure 1). Based on the dynamics of the regional proportion of neurons with information-coding ability, we could group the 29 recorded regions (with more than 100 recorded neurons) into three region clusters. Cluster 1 was composed of sensory areas for olfactory, cluster 2 included many association areas, whereas cluster 3 included motor-related regions (Figure 2B). From region clusters 1 to 3, we observed progressive increase from more sensory （sample ratio） to more categorical encoding. We also observed temporal progression for this sensory to categorical transformation, especially during the later delay period and lick-action periods. In the error trials, neurons showed reduced but correct encoding of sensory information during the delay period, whereas reversed encoding of categorical information during the action period (Figure 3). Spike correlogram revealed strong directional functional coupling at ten-millisecond time scale in the neuronal pairs, especially those showing congruent odor selectivity. The cross-region functionally coupling showed differential dynamics in three region clusters, in a manner correlated with information-maintenance ability (Figure 4, 5). Our results revealed the brain-wide dynamics in sensory-to-category transformation in the brain and further underscored the importance of information-specific functional coupling in cognition.