Context-dependent relationships between locus coeruleus firing patterns and coordinated neural activity in the anterior cingulate cortex

  1. Siddhartha Joshi  Is a corresponding author
  2. Joshua I Gold
  1. Baylor College of Medicine, United States
  2. University of Pennsylvania, United States


Ascending neuromodulatory projections from the locus coeruleus (LC) affect cortical neural networks via the release of norepinephrine (NE). However, the exact nature of these neuromodulatory effects on neural activity patterns in vivo is not well understood. Here we show that in awake monkeys, LC activation is associated with changes in coordinated activity patterns in the anterior cingulate cortex (ACC). These relationships, which are largely independent of changes in firing rates of individual ACC neurons, depend on the type of LC activation: ACC pairwise correlations tend to be reduced when ongoing (baseline) LC activity increases but enhanced when external events evoke transient LC responses. Both relationships covary with pupil changes that reflect LC activation and arousal. These results suggest that modulations of information processing that reflect changes in coordinated activity patterns in cortical networks can result partly from ongoing, context-dependent, arousal-related changes in activation of the LC-NE system.

Data availability

Data and Matlab code for all figures in this manuscript are available at:

Article and author information

Author details

  1. Siddhartha Joshi

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0529-9430
  2. Joshua I Gold

    Department of Neuroscience, University of Pennsylvania, Philadelphia, United States
    Competing interests
    Joshua I Gold, Senior editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6018-0483


National Institutes of Health (R21 MH107001)

  • Joshua I Gold

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: All animal training, surgery and experimental procedures were performed in accordance withthe NIH's Guide for the Care and Use of Laboratory Animals and were approved by the Universityof Pennsylvania Institutional Animal Care and Use Committee (protocol 806027).

Reviewing Editor

  1. Erin L Rich, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: September 25, 2020
  2. Preprint posted: September 28, 2020 (view preprint)
  3. Accepted: December 16, 2021
  4. Accepted Manuscript published: January 7, 2022 (version 1)
  5. Version of Record published: January 18, 2022 (version 2)


© 2022, Joshi & Gold

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


  • 1,747
    Page views
  • 291
  • 8

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Siddhartha Joshi
  2. Joshua I Gold
Context-dependent relationships between locus coeruleus firing patterns and coordinated neural activity in the anterior cingulate cortex
eLife 11:e63490.

Further reading

    1. Neuroscience
    Xiaosha Wang, Bijun Wang, Yanchao Bi
    Research Article Updated

    One signature of the human brain is its ability to derive knowledge from language inputs, in addition to nonlinguistic sensory channels such as vision and touch. How does human language experience modulate the mechanism by which semantic knowledge is stored in the human brain? We investigated this question using a unique human model with varying amounts and qualities of early language exposure: early deaf adults who were born to hearing parents and had reduced early exposure and delayed acquisition of any natural human language (speech or sign), with early deaf adults who acquired sign language from birth as the control group that matches on nonlinguistic sensory experiences. Neural responses in a semantic judgment task with 90 written words that were familiar to both groups were measured using fMRI. The deaf group with reduced early language exposure, compared with the deaf control group, showed reduced semantic sensitivity, in both multivariate pattern (semantic structure encoding) and univariate (abstractness effect) analyses, in the left dorsal anterior temporal lobe (dATL). These results provide positive, causal evidence that language experience drives the neural semantic representation in the dATL, highlighting the roles of language in forming human neural semantic structures beyond nonverbal sensory experiences.

    1. Neuroscience
    Ayako Yamaguchi, Manon Peltier
    Research Article Updated

    Across phyla, males often produce species-specific vocalizations to attract females. Although understanding the neural mechanisms underlying behavior has been challenging in vertebrates, we previously identified two anatomically distinct central pattern generators (CPGs) that drive the fast and slow clicks of male Xenopus laevis, using an ex vivo preparation that produces fictive vocalizations. Here, we extended this approach to four additional species, X. amieti, X. cliivi, X. petersii, and X. tropicalis, by developing ex vivo brain preparation from which fictive vocalizations are elicited in response to a chemical or electrical stimulus. We found that even though the courtship calls are species-specific, the CPGs used to generate clicks are conserved across species. The fast CPGs, which critically rely on reciprocal connections between the parabrachial nucleus and the nucleus ambiguus, are conserved among fast-click species, and slow CPGs are shared among slow-click species. In addition, our results suggest that testosterone plays a role in organizing fast CPGs in fast-click species, but not in slow-click species. Moreover, fast CPGs are not inherited by all species but monopolized by fast-click species. The results suggest that species-specific calls of the genus Xenopus have evolved by utilizing conserved slow and/or fast CPGs inherited by each species.