Behavioral state-dependent norepinephrine dynamics in the primary somatosensory and prefrontal cortices during...

Animals must integrate sensory information, ignore behaviorally irrelevant stimuli, and respond to behaviorally relevant stimuli to find food, find mates, avoid predators, and ultimately survive. In mammals, these goal-directed behaviors require the coordinated activity of many brain regions, including sensory and prefrontal cortices as well as neuromodulatory brainstem nuclei like the locus coeruleus (LC), which is the brain's primary source of norepinephrine. Norepinephrine resulting from LC activity and arousal indexed by pupil size exert strong influences on goal-directed behavior. We explored the relationships between pupil size, cortical noradrenergic dynamics, and behavior in a tactile signal detection task. We monitored pupil dynamics and fluorescent GRAB_NE signals in somatosensory and prefrontal cortices simultaneously during task execution and found that pupil size and synchronization of GRAB_NE signals at baseline were strong predictors of whether animals chose to respond but not baseline cortical GRAB_NE levels. We also employed a generalized linear model - hidden Markov model (GLM-HMM) framework to identify distinct, stable behavioral states throughout the task that optimally account for task performance. We found distinct psychometric curves, task-evoked pupil dynamics, and cortical NE dynamics across these behavioral states.