Behavioral state-dependent norepinephrine dynamics in the primary somatosensory and prefrontal cortices during tactile detection tasks

Abstract

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 and neuromodulatory brainstem nuclei like the locus coeruleus (LC), which is the brains primary source of norepinephrine (NE). NE release 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 GRABNE signals in somatosensory and medial prefrontal cortices simultaneously during task execution and found that pupil size and synchronization of GRABNE signals at baseline were strong predictors of whether animals chose to respond. Baseline and post-reward cortical GRABNE levels varied strongly with pupil-linked arousal. We also employed a generalized linear model - hidden Markov model (GLM-HMM) framework to identify distinct, stable behavioral states throughout the task that characterize task performance. We found distinct psychometric curves, task-related pupil dynamics, and cortical NE dynamics across these behavioral states. Significance StatementBehavioral state strongly shapes goal-directed behavior, which in turn depends on the coordinated activity of distributed brain regions, including the sensory and prefrontal cortices. By simultaneously measuring pupil size and cortical noradrenergic dynamics, and by identifying psychophysically distinct behavioral states during a tactile detection task, this study establishes links between pupil-linked arousal, norepinephrine signaling in somatosensory and prefrontal cortices, and trial outcomes. These findings provide new insight into how the locus coeruleus - norepinephrine system regulates perception and decision-making.