Differential attentional control mechanisms by two distinct noradrenergic coeruleo-frontal cortical pathways
Name
29080.full.pdf
Description
Published version
Size
1.99 MB
Format
Adobe PDF
Checksum (MD5)
d9c0bfb19af53340cc452eb8fe1f3013
Author(s)
Bari, Andrea
Xu, Sangyu
Pignatelli, Michele
Takeuchi, Daigo
Feng, Jiesi
Li, Yulong
Tonegawa, Susumu
Date Issued
2020
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Version
Final published version
Abstract
© 2020 National Academy of Sciences. All rights reserved. The attentional control of behavior is a higher-order cognitive function that operates through attention and response inhibition. The locus coeruleus (LC), the main source of norepinephrine in the brain, is considered to be involved in attentional control by modulating the neuronal activity of the prefrontal cortex (PFC). However, evidence for the causal role of LC activity in attentional control remains elusive. Here, by using behavioral and optogenetic techniques, we investigate the effect of LC neuron activation or inhibition in operant tests measuring attention and response inhibition (i.e., a measure of impulsive behavior). We show that LC neuron stimulation increases goal-directed attention and decreases impulsivity, while its suppression exacerbates distractibility and increases impulsive responding. Remarkably, we found that attention and response inhibition are under the control of two divergent projections emanating from the LC: one to the dorso-medial PFC and the other to the ventro-lateral orbitofrontal cortex, respectively. These findings are especially relevant for those pathological conditions characterized by attention deficits and elevated impulsivity.
MIT Department
RIKEN-MIT Center for Neural Circuit Genetics
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Howard Hughes Medical Institute
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.2015635117
