McBurney-Lin, J. | bioRxiv Science

bioRxiv2022

The locus coeruleus mediates behavioral flexibility

Behavioral flexibility refers to the ability to adjust behavioral strategies in response to changing environmental contingencies. A major hypothesis in the field posits that the activity of neurons in the locus coeruleus (LC) plays an important role in mediating behavioral flexibility. To test this hypothesis, we developed a novel context-dependent bilateral tactile detection task where mice responded to left and right whisker deflections in a rule-dependent manner and exhibited varying degrees of flexible switching behavior. Recording from optogenetically-tagged neurons in the LC during task performance revealed a prominent graded correlation between baseline LC activity and behavioral flexibility, where higher baseline activity following a rule change was associated with faster behavioral switching to the new rule. Increasing baseline LC activity with optogenetic activation improved task performance and accelerated task switching. Overall, our study provides strong evidence to demonstrate that LC activity mediates behavioral flexibility.

neuroscience↗

bioRxiv2020

Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection

The brain neuromodulatory systems heavily influence behavioral and cognitive processes. Previous work has shown that norepinephrine (NE), a classic neuromodulator mainly derived from the locus coeruleus (LC), enhances neuronal responses to sensory stimuli. However, the role of the LC-NE system in modulating perceptual task performance is not well understood. In addition, systemic perturbation of NE signaling has often been proposed to specifically target the LC in functional studies, yet the assumption that localized (specific) and systemic (nonspecific) perturbations of LC-NE have the same behavioral impact remains largely untested. In this study, we trained mice to perform a head-fixed, quantitative tactile detection task, and administered an 2 adrenergic receptor agonist or antagonist to pharmacologically down- or up-regulate LC-NE activity, respectively. We addressed the outstanding question of how bidirectional perturbations of LC-NE activity affect tactile detection, and tested whether localized and systemic drug treatments exert the same behavioral effects. We found that both localized and systemic suppression of LC-NE impaired tactile detection by reducing motivation. Surprisingly, while locally activating LC-NE enabled mice to perform in a near-optimal regime, systemic activation impaired behavior by promoting impulsivity. Our results demonstrate that localized silencing and activation of LC-NE differentially affect tactile detection, and that localized and systemic NE activation induce distinct behavioral changes.

neuroscience↗