Top-down mechanisms and modulation of flexible tactile discrimination

ABSTRACT In contrast to fixed stimulus-response associations, flexible behavior allows organisms to respond differently to the same stimuli depending on their current goals. Given a relatively stable structure of the brain, how can organisms implement different stimulus-response associations in a context-dependent, goal-directed manner? While previous work has investigated the roles of various brain regions in flexible switching behavior, we still lack fundamental understanding of how neural signals propagating within and between brain regions underlie this important cognitive function. Our proposal focuses on the interactions between three different brain regions in mediating rule switching: the locus coeruleus, the orbitofrontal cortex, and the somatosensory cortex. We test specific hypotheses regarding the contributions of each of these circuits by combining pathway-specific perturbations with cellular-resolution neurophysiological recordings in task-performing mice. Altogether, we will provide a unifying framework for how the locus coeruleus, orbitofrontal cortex, and somatosensory cortex coordinate to implement flexible goal-directed behavior.