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

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 arousa...

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Main Authors: Lindsay Collins, John Francis, Brett Emanuel, David A McCormick
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-04-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/81826
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author Lindsay Collins
John Francis
Brett Emanuel
David A McCormick
author_facet Lindsay Collins
John Francis
Brett Emanuel
David A McCormick
author_sort Lindsay Collins
collection DOAJ
description 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.
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spelling doaj.art-07255aef24f5454d90230396f4e2aadf2023-06-02T16:04:26ZengeLife Sciences Publications LtdeLife2050-084X2023-04-011210.7554/eLife.81826Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortexLindsay Collins0https://orcid.org/0000-0002-8588-2780John Francis1Brett Emanuel2https://orcid.org/0009-0001-8494-728XDavid A McCormick3https://orcid.org/0000-0002-9803-8335Institute of Neuroscience, University of Oregon, Eugene, United StatesInstitute of Neuroscience, University of Oregon, Eugene, United StatesInstitute of Neuroscience, University of Oregon, Eugene, United StatesInstitute of Neuroscience, University of Oregon, Eugene, United StatesFluctuations 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.https://elifesciences.org/articles/81826noradrenalineacetylcholineaxon
spellingShingle Lindsay Collins
John Francis
Brett Emanuel
David A McCormick
Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
eLife
noradrenaline
acetylcholine
axon
title Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
title_full Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
title_fullStr Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
title_full_unstemmed Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
title_short Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex
title_sort cholinergic and noradrenergic axonal activity contains a behavioral state signal that is coordinated across the dorsal cortex
topic noradrenaline
acetylcholine
axon
url https://elifesciences.org/articles/81826
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