Context-dependent relationships between locus coeruleus firing patterns and coordinated neural activity in the anterior cingulate cortex
Abstract
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:https://github.com/TheGoldLab/LC_ACC_paper_Joshi_Gold_2021.git
Article and author information
Author details
Funding
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.
Reviewing Editor
- Erin L Rich, Icahn School of Medicine at Mount Sinai, United States
Ethics
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).
Version history
- Received: September 25, 2020
- Preprint posted: September 28, 2020 (view preprint)
- Accepted: December 16, 2021
- Accepted Manuscript published: January 7, 2022 (version 1)
- Version of Record published: January 18, 2022 (version 2)
Copyright
© 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.
Metrics
-
- 2,133
- views
-
- 327
- downloads
-
- 23
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurological and systemic comorbidities, including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently, we showed the postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests that glutamatergic–cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.
-
- Neuroscience
Improving our understanding of autism, ADHD, dyslexia and other neurodevelopmental conditions requires collaborations between genetics, psychiatry, the social sciences and other fields of research.