Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
- University of Oregon, United States
Abstract
Fluctuations in brain and behavioral state are supported by broadly projecting neuromodulatory systems. In this study, we use mesoscale two-photon calcium imaging to examine spontaneous activity of cholinergic and noradrenergic axons in awake mice in order to determine the interaction between arousal/movement state transitions and neuromodulatory activity across the dorsal cortex at distances separated by up to 4 mm. We confirm that GCaMP6s activity within axonal projections of both basal forebrain cholinergic and locus coeruleus noradrenergic neurons track arousal, indexed as pupil diameter, and changes in behavioral engagement, as reflected by bouts of whisker movement and/or locomotion. The broad coordination in activity between even distant axonal segments indicates that both of these systems can communicate, in part, through a global signal, especially in relation to changes in behavioral state. In addition to this broadly coordinated activity, we also find evidence that a subpopulation of both cholinergic and noradrenergic axons may exhibit heterogeneity in activity that appears to be independent of our measures of behavioral state. By monitoring the activity of cholinergic interneurons in the cortex we found that a subpopulation of these cells also exhibit state-dependent (arousal/movement) activity. These results demonstrate that cholinergic and noradrenergic systems provide a prominent and broadly synchronized signal related to behavioral state, and therefore may contribute to state-dependent cortical activity and excitability.
Data availability
Data files have been deposited to the Open Science Framework (https://osf.io/rwtpu/). Custom Matlab codes can be found at www.github.com/lncollins91/ACh_NA_VCIN.
Article and author information
Author details
Funding
National Institutes of Health (R35NS097287)
- David A McCormick
National Institutes of Health (R01NS118461)
- David A McCormick
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sacha B Nelson, Brandeis University, United States
Ethics
Animal experimentation: All experiments were approved by the University of Oregon Institutional Animal Care and Use Committee and performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All surgery was performed under isoflurane anesthesia, and every effort was made to minimize suffering.
Version history
- Preprint posted: July 13, 2022 (view preprint)
- Received: July 13, 2022
- Accepted: April 24, 2023
- Accepted Manuscript published: April 27, 2023 (version 1)
- Version of Record published: June 2, 2023 (version 2)
Copyright
© 2023, Collins et al.
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.
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Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
eLife 12:e81826.
https://doi.org/10.7554/eLife.81826
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