Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex

Abstract
Data availability
Article and author information
Metrics

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.

The following data sets were generated

(2023) Cholinergic and noradrenergic axon imaging
Open Science Framework, rwtpu.

https://osf.io/rwtpu/

Article and author information

Author details

Lindsay Collins

Institute of Neuroscience, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
John Francis

Institute of Neuroscience, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Brett Emanuel

Institute of Neuroscience, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
David A McCormick

Institute of Neuroscience, University of Oregon, Oregon, United States

For correspondence
davidmc@uoregon.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9803-8335

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.

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.

Copyright

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.