Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
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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Further reading
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Probing memory of a complex visual image within a few hundred milliseconds after its disappearance reveals significantly greater fidelity of recall than if the probe is delayed by as little as a second. Classically interpreted, the former taps into a detailed but rapidly decaying visual sensory or ‘iconic’ memory (IM), while the latter relies on capacity-limited but comparatively stable visual working memory (VWM). While iconic decay and VWM capacity have been extensively studied independently, currently no single framework quantitatively accounts for the dynamics of memory fidelity over these time scales. Here, we extend a stationary neural population model of VWM with a temporal dimension, incorporating rapid sensory-driven accumulation of activity encoding each visual feature in memory, and a slower accumulation of internal error that causes memorized features to randomly drift over time. Instead of facilitating read-out from an independent sensory store, an early cue benefits recall by lifting the effective limit on VWM signal strength imposed when multiple items compete for representation, allowing memory for the cued item to be supplemented with information from the decaying sensory trace. Empirical measurements of human recall dynamics validate these predictions while excluding alternative model architectures. A key conclusion is that differences in capacity classically thought to distinguish IM and VWM are in fact contingent upon a single resource-limited WM store.
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Our ability to recall details from a remembered image depends on a single mechanism that is engaged from the very moment the image disappears from view.