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

  1. Lindsay Collins
  2. John Francis
  3. Brett Emanuel
  4. David A McCormick  Is a corresponding author
  1. 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.

The following data sets were generated

Article and author information

Author details

  1. Lindsay Collins

    Institute of Neuroscience, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. John Francis

    Institute of Neuroscience, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Brett Emanuel

    Institute of Neuroscience, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. 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.
    ORCID icon "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.

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Publication history

  1. Received: July 13, 2022
  2. Accepted: April 24, 2023
  3. Accepted Manuscript published: April 27, 2023 (version 1)

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.

Metrics

  • 812
    Page views
  • 239
    Downloads
  • 0
    Citations

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. Lindsay Collins
  2. John Francis
  3. Brett Emanuel
  4. David A McCormick
(2023)
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

Further reading

    1. Neuroscience
    Abraham Katzen, Hui-Kuan Chung ... Shawn R Lockery
    Research Article Updated

    In value-based decision making, options are selected according to subjective values assigned by the individual to available goods and actions. Despite the importance of this faculty of the mind, the neural mechanisms of value assignments, and how choices are directed by them, remain obscure. To investigate this problem, we used a classic measure of utility maximization, the Generalized Axiom of Revealed Preference, to quantify internal consistency of food preferences in Caenorhabditis elegans, a nematode worm with a nervous system of only 302 neurons. Using a novel combination of microfluidics and electrophysiology, we found that C. elegans food choices fulfill the necessary and sufficient conditions for utility maximization, indicating that nematodes behave as if they maintain, and attempt to maximize, an underlying representation of subjective value. Food choices are well-fit by a utility function widely used to model human consumers. Moreover, as in many other animals, subjective values in C. elegans are learned, a process we find requires intact dopamine signaling. Differential responses of identified chemosensory neurons to foods with distinct growth potentials are amplified by prior consumption of these foods, suggesting that these neurons may be part of a value-assignment system. The demonstration of utility maximization in an organism with a very small nervous system sets a new lower bound on the computational requirements for utility maximization and offers the prospect of an essentially complete explanation of value-based decision making at single neuron resolution in this organism.

    1. Neuroscience
    Yuan-hao Wu, Ella Podvalny, Biyu J He
    Research Article Updated

    While there is a wealth of knowledge about core object recognition—our ability to recognize clear, high-contrast object images—how the brain accomplishes object recognition tasks under increased uncertainty remains poorly understood. We investigated the spatiotemporal neural dynamics underlying object recognition under increased uncertainty by combining MEG and 7 Tesla (7T) fMRI in humans during a threshold-level object recognition task. We observed an early, parallel rise of recognition-related signals across ventral visual and frontoparietal regions that preceded the emergence of category-related information. Recognition-related signals in ventral visual regions were best explained by a two-state representational format whereby brain activity bifurcated for recognized and unrecognized images. By contrast, recognition-related signals in frontoparietal regions exhibited a reduced representational space for recognized images, yet with sharper category information. These results provide a spatiotemporally resolved view of neural activity supporting object recognition under uncertainty, revealing a pattern distinct from that underlying core object recognition.