Thalamic control of sensory selection in divided attention

How the brain selects appropriate sensory inputs and suppresses distractors is a central unsolved mystery in neuroscience. Given the well-established role of prefrontal cortex (PFC) in executive function(1), its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection(2–5). To test this idea and more generally dissect the circuits underlying sensory selection, we developed a cross-modal divided attention task in mice enabling genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally-precise window, the ability of mice to appropriately select between conflicting visual and auditory stimuli was diminished. Surprisingly, equivalent sensory thalamo-cortical manipulations showed that behavior was causally dependent on PFC interactions with sensory thalamus, not cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed via subnetwork-specific bi-directional optogenetic manipulations. Through a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Combined, our experiments introduce a new subcortical model of sensory selection, where prefrontal cortex biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing.