Distinct 'driving' versus 'modulatory' influences of different visual corticothalamic pathways

Higher-order (HO) thalamic nuclei interact extensively with the cerebral cortex and are innervated by excitatory corticothalamic (CT) populations in layers 5 and 6. While these distinct CT projections have long been thought to have different functional influences on the HO thalamus, this has never been directly tested. By optogenetically inactivating different CT populations in the primary visual cortex (V1) of awake mice, we demonstrate that layer 5, but not layer 6, CT projections drive visual responses in the HO visual pulvinar, even while both pathways provide retinotopic, baseline excitation to their thalamic targets. Inactivating the superior colliculus also suppressed visual responses in the pulvinar, demonstrating that cortical layer 5 and subcortical inputs both contribute to HO visual thalamic activity - even at the level of putative single neurons. Altogether, these results indicate a functional division of driver and modulator CT pathways from V1 to the visual thalamus in vivo.