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Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo
Norepinephrine is a monoamine neurotransmitter with a wide repertoire of physiological roles in the peripheral and central nervous systems. There are, however, no experimental means to study functional properties of individual noradrenergic synapses in the brain. Development of new approaches for im...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053466/ https://www.ncbi.nlm.nih.gov/pubmed/30026491 http://dx.doi.org/10.1038/s41467-018-05075-x |
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author | Dunn, Matthew Henke, Adam Clark, Samuel Kovalyova, Yekaterina Kempadoo, Kimberly A. Karpowicz, Richard J. Kandel, Eric R. Sulzer, David Sames, Dalibor |
author_facet | Dunn, Matthew Henke, Adam Clark, Samuel Kovalyova, Yekaterina Kempadoo, Kimberly A. Karpowicz, Richard J. Kandel, Eric R. Sulzer, David Sames, Dalibor |
author_sort | Dunn, Matthew |
collection | PubMed |
description | Norepinephrine is a monoamine neurotransmitter with a wide repertoire of physiological roles in the peripheral and central nervous systems. There are, however, no experimental means to study functional properties of individual noradrenergic synapses in the brain. Development of new approaches for imaging synaptic neurotransmission is of fundamental importance to study specific synaptic changes that occur during learning, behavior, and pathological processes. Here, we introduce fluorescent false neurotransmitter 270 (FFN270), a fluorescent tracer of norepinephrine. As a fluorescent substrate of the norepinephrine and vesicular monoamine transporters, FFN270 labels noradrenergic neurons and their synaptic vesicles, and enables imaging synaptic vesicle content release from specific axonal sites in living rodents. Combining FFN270 imaging and optogenetic stimulation, we find heterogeneous release properties of noradrenergic synapses in the somatosensory cortex, including low and high releasing populations. Through systemic amphetamine administration, we observe rapid release of cortical noradrenergic vesicular content, providing insight into the drug’s effect. |
format | Online Article Text |
id | pubmed-6053466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60534662018-07-25 Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo Dunn, Matthew Henke, Adam Clark, Samuel Kovalyova, Yekaterina Kempadoo, Kimberly A. Karpowicz, Richard J. Kandel, Eric R. Sulzer, David Sames, Dalibor Nat Commun Article Norepinephrine is a monoamine neurotransmitter with a wide repertoire of physiological roles in the peripheral and central nervous systems. There are, however, no experimental means to study functional properties of individual noradrenergic synapses in the brain. Development of new approaches for imaging synaptic neurotransmission is of fundamental importance to study specific synaptic changes that occur during learning, behavior, and pathological processes. Here, we introduce fluorescent false neurotransmitter 270 (FFN270), a fluorescent tracer of norepinephrine. As a fluorescent substrate of the norepinephrine and vesicular monoamine transporters, FFN270 labels noradrenergic neurons and their synaptic vesicles, and enables imaging synaptic vesicle content release from specific axonal sites in living rodents. Combining FFN270 imaging and optogenetic stimulation, we find heterogeneous release properties of noradrenergic synapses in the somatosensory cortex, including low and high releasing populations. Through systemic amphetamine administration, we observe rapid release of cortical noradrenergic vesicular content, providing insight into the drug’s effect. Nature Publishing Group UK 2018-07-19 /pmc/articles/PMC6053466/ /pubmed/30026491 http://dx.doi.org/10.1038/s41467-018-05075-x Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Dunn, Matthew Henke, Adam Clark, Samuel Kovalyova, Yekaterina Kempadoo, Kimberly A. Karpowicz, Richard J. Kandel, Eric R. Sulzer, David Sames, Dalibor Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
title | Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
title_full | Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
title_fullStr | Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
title_full_unstemmed | Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
title_short | Designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
title_sort | designing a norepinephrine optical tracer for imaging individual noradrenergic synapses and their activity in vivo |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053466/ https://www.ncbi.nlm.nih.gov/pubmed/30026491 http://dx.doi.org/10.1038/s41467-018-05075-x |
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