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Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection

Jim McBurney-Lin, Yina Sun, Lucas S. Tortorelli, Quynh Anh Nguyen, Sachiko Haga-Yamanaka, View ORCID ProfileHongdian Yang
doi: https://doi.org/10.1101/2020.04.22.052043
Jim McBurney-Lin
1Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA
2Neuroscience Graduate Program, University of California, Riverside, CA 92521, USA
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Yina Sun
1Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA
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Lucas S. Tortorelli
1Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA
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Quynh Anh Nguyen
1Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA
2Neuroscience Graduate Program, University of California, Riverside, CA 92521, USA
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Sachiko Haga-Yamanaka
1Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA
2Neuroscience Graduate Program, University of California, Riverside, CA 92521, USA
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Hongdian Yang
1Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA 92521, USA
2Neuroscience Graduate Program, University of California, Riverside, CA 92521, USA
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  • ORCID record for Hongdian Yang
  • For correspondence: hongdian@ucr.edu
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Abstract

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 α2 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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 24, 2020.
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Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection
Jim McBurney-Lin, Yina Sun, Lucas S. Tortorelli, Quynh Anh Nguyen, Sachiko Haga-Yamanaka, Hongdian Yang
bioRxiv 2020.04.22.052043; doi: https://doi.org/10.1101/2020.04.22.052043
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Bidirectional pharmacological perturbations of the noradrenergic system differentially affect tactile detection
Jim McBurney-Lin, Yina Sun, Lucas S. Tortorelli, Quynh Anh Nguyen, Sachiko Haga-Yamanaka, Hongdian Yang
bioRxiv 2020.04.22.052043; doi: https://doi.org/10.1101/2020.04.22.052043

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