Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in behavior

The insular cortex (insula) is known to play a modulatory role in feeding and drink-ing. Previous studies have revealed anterior-posterior differences of subcortical projections and roles for the insula, yet the anatomical and functional heteroge-neity among the cortical layers remains poorly understood. Here, we show that layer 5 of the mouse dysgranular insula has two distinct neuronal subpopulations along the entire anterior-posterior axis: The L5a population, expressing NECAB1, projects bilaterally to the lateral and capsular divisions of the central amygdala, and the L5b population, expressing CTIP2, projects ipsilaterally to the parasub-thalamic nucleus and the medial division of the central amygdala. Optogenetically activating L5a and L5b neuronal populations in thirsty male mice led to sup-pressed and facilitated water spout licking, respectively, without avoidance against or preference for the spout paired with the opto-stimulation. Our results suggest sublayer-specific bidirectional modulatory roles of insula layer 5 in the motivational aspect of appetitive behavior.

Automated summary

This study reveals that there are two distinct neuronal subpopulations in layer 5 of the mouse dysgranular insula, namely L5a and L5b. L5a cells project bilaterally to the lateral and capsular divisions of the central amygdala, while L5b cells project ipsilaterally to the parasubthalamic nucleus and the medial division of the central amygdala. Activation of L5a and L5b cells leads to suppressed and facilitated water drinking behavior in thirsty mice, respectively.