Prefrontal and Midbrain Contributions to Fast Executive Control of Behavior in the Rat

Flexible control of behavior based on the relevant environmental context is a fundamental component of adaptive behavior. The capability to rapidly switch between different sensorimotor mappings to achieve the current goal is called executive control, and is predominantly studied in primates. To probe fast executive control using the tools available in rodents, we developed a novel rat behavior in which subjects are cued, on each trial, to apply a sensorimotor association to orient either toward a visual target (“Pro”) or away from it (“Anti”). Multiple behavioral asymmetries suggested that Anti behavior is cognitively demanding while Pro is easier to learn and perform. This is consistent with a prominent hypothesis in the primate literature that Anti required prefrontal cortex (PFC), whereas Pro could be mediated by the midbrain superior colliculus (SC). Pharmacological inactivation of rat medial PFC supported its expected role in Anti. Remarkably, bilateral SC inactivation substantially impaired Anti while leaving Pro essentially intact. Moreover, SC inactivation eliminated the performance cost of switching from Anti to Pro tasks. These results suggest a more diffuse network underlying response inhibition and task switching, including PFC and SC. Characterization of neural signatures underlying flexible sensorimotor transformation revealed dynamic task-relevant signals in the SC neurons during the delay period, similar to PFC neurons. We tested the causal requirement of this task set maintenance activity in the SC, and found a selective Anti impairment after optogenetic inactivation in bilateral SC during the delay. Together, our results establish a rodent model of rapid sensorimotor remapping and suggest a critical role for SC in maintaining a cognitively demanding task set to flexibly map sensory stimuli to correct motor outputs. iii