Evidence for Layer-Specific Connectional Heterogeneity in the Mouse Auditory Corticocollicular System

The auditory cortex (AC) sends long-range projections to virtually all subcortical auditory structures. One of the largest and most complex of these-the projection between AC and inferior colliculus (IC; the corticocollicular pathway)-originates from layer 5 and deep layer 6. Though previous work has shown that these two corticocollicular projection systems have different physiological properties and network connectivities, their functional organization is poorly understood. Here, using a combination of traditional and viral tracers combined with in vivo imaging in both sexes of the mouse, we observed that layer 5 and layer 6 corticocollicular neurons differ in their areas of origin and termination patterns. Layer 5 corticocollicular neurons are concentrated in primary AC, while layer 6 corticocollicular neurons emanate from broad auditory and limbic areas in the temporal cortex. In addition, layer 5 sends dense projections of both small and large (>1 mu m(2) area) terminals to all regions of nonlemniscal IC, while layer 6 sends small terminals to the most superficial 50-100 mu m of the IC. These findings suggest that layer 5 and 6 corticocollicular projections are optimized to play distinct roles in corticofugal modulation. Layer 5 neurons provide strong, rapid, and unimodal feedback to the nonlemniscal IC, while layer 6 neurons provide heteromodal and limbic modulation diffusely to the nonlemniscal IC. Such organizational diversity in the corticocollicular pathway may help to explain the heterogeneous effects of corticocollicular manipulations and, given similar diversity in corticothalamic pathways, may be a general principle in top-down modulation.