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Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus
The locus coeruleus (LC) provides the principal supply of noradrenaline (NA) to the brain, thereby modulating an array of brain functions. The release of NA, and therefore its impact on the brain, is governed by LC neuronal excitability. Glutamatergic axons, from various brain regions, topographical...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557397/ https://www.ncbi.nlm.nih.gov/pubmed/37391270 http://dx.doi.org/10.1111/joa.13922 |
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author | Kelly, Louise Brown, Christopher Gibbard, Adina G. Jackson, Torquil Swinny, Jerome D. |
author_facet | Kelly, Louise Brown, Christopher Gibbard, Adina G. Jackson, Torquil Swinny, Jerome D. |
author_sort | Kelly, Louise |
collection | PubMed |
description | The locus coeruleus (LC) provides the principal supply of noradrenaline (NA) to the brain, thereby modulating an array of brain functions. The release of NA, and therefore its impact on the brain, is governed by LC neuronal excitability. Glutamatergic axons, from various brain regions, topographically innervate different LC sub‐domains and directly alter LC excitability. However, it is currently unclear whether glutamate receptor sub‐classes, such as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors, are divergently expressed throughout the LC. Immunohistochemistry and confocal microscopy were used to identify and localise individual GluA subunits in the mouse LC. Whole‐cell patch clamp electrophysiology and subunit‐preferring ligands were used to assess their impact on LC spontaneous firing rate (FR). GluA1 immunoreactive clusters were associated with puncta immunoreactive for VGLUT2 on somata, and VGLUT1 on distal dendrites. GluA4 was associated with these synaptic markers only in the distal dendrites. No specific signal was detected for the GluA2‐3 subunits. The GluA1/2 receptor agonist (S)‐CPW 399 increased LC FR, whilst the GluA1/3 receptor antagonist philanthotoxin‐74 decreased it. 4‐[2‐(phenylsulfonylamino)ethylthio]‐2,6‐difluoro‐phenoxyacetamide (PEPA), a positive allosteric modulator of GluA3/4 receptors, had no significant effect on spontaneous FR. The data suggest distinct AMPA receptor subunits are targeted to different LC afferent inputs and have contrasting effects on spontaneous neuronal excitability. This precise expression profile could be a mechanism for LC neurons to integrate diverse information contained in various glutamate afferents. |
format | Online Article Text |
id | pubmed-10557397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105573972023-10-07 Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus Kelly, Louise Brown, Christopher Gibbard, Adina G. Jackson, Torquil Swinny, Jerome D. J Anat Original Articles The locus coeruleus (LC) provides the principal supply of noradrenaline (NA) to the brain, thereby modulating an array of brain functions. The release of NA, and therefore its impact on the brain, is governed by LC neuronal excitability. Glutamatergic axons, from various brain regions, topographically innervate different LC sub‐domains and directly alter LC excitability. However, it is currently unclear whether glutamate receptor sub‐classes, such as α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors, are divergently expressed throughout the LC. Immunohistochemistry and confocal microscopy were used to identify and localise individual GluA subunits in the mouse LC. Whole‐cell patch clamp electrophysiology and subunit‐preferring ligands were used to assess their impact on LC spontaneous firing rate (FR). GluA1 immunoreactive clusters were associated with puncta immunoreactive for VGLUT2 on somata, and VGLUT1 on distal dendrites. GluA4 was associated with these synaptic markers only in the distal dendrites. No specific signal was detected for the GluA2‐3 subunits. The GluA1/2 receptor agonist (S)‐CPW 399 increased LC FR, whilst the GluA1/3 receptor antagonist philanthotoxin‐74 decreased it. 4‐[2‐(phenylsulfonylamino)ethylthio]‐2,6‐difluoro‐phenoxyacetamide (PEPA), a positive allosteric modulator of GluA3/4 receptors, had no significant effect on spontaneous FR. The data suggest distinct AMPA receptor subunits are targeted to different LC afferent inputs and have contrasting effects on spontaneous neuronal excitability. This precise expression profile could be a mechanism for LC neurons to integrate diverse information contained in various glutamate afferents. John Wiley and Sons Inc. 2023-06-30 /pmc/articles/PMC10557397/ /pubmed/37391270 http://dx.doi.org/10.1111/joa.13922 Text en © 2023 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Kelly, Louise Brown, Christopher Gibbard, Adina G. Jackson, Torquil Swinny, Jerome D. Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus |
title | Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus |
title_full | Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus |
title_fullStr | Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus |
title_full_unstemmed | Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus |
title_short | Subunit‐specific expression and function of AMPA receptors in the mouse locus coeruleus |
title_sort | subunit‐specific expression and function of ampa receptors in the mouse locus coeruleus |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557397/ https://www.ncbi.nlm.nih.gov/pubmed/37391270 http://dx.doi.org/10.1111/joa.13922 |
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