Context-dependent and dynamic functional influence of corticothalamic pathways to first- and higher-order visual thalamus

Layer 6 (L6) is the sole purveyor of corticothalamic (CT) feedback to first-order thalamus and also sends projections to higher-order thalamus, yet how it engages the full corticothalamic circuit to contribute to sensory processing in an awake animal remains un-known. We sought to elucidate the functional impact of L6CT pro-jections from the primary visual cortex to the dorsolateral geniculate nucleus (first-order) and pulvinar (higher-order) using optogenetics and extracellular electrophysiology in awake mice. While sustained L6CT photostimulation suppresses activity in both visual thalamic nuclei in vivo, moderate-frequency (10 Hz) stimulation powerfully facilitates thalamic spiking. We show that each stimulation paradigm differentially influences the balance between monosynaptic excit-atory and disynaptic inhibitory corticothalamic pathways to the dor-solateral geniculate nucleus and pulvinar, as well as the prevalence of burst versus tonic firing. Altogether, our results support a model in which L6CTs modulate first-and higher-order thalamus through par-allel excitatory and inhibitory pathways that are highly dynamic and context-dependent.