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Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels
The activity of serotonin (5-HT) neurons is critical for mood regulation. In a mouse model of chronic social isolation, a known risk factor for depressive illness, we show that 5-HT neurons in the dorsal raphe nucleus are less responsive to stimulation. Probing the responsible cellular mechanisms pi...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119885/ https://www.ncbi.nlm.nih.gov/pubmed/27874831 http://dx.doi.org/10.7554/eLife.21416 |
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author | Sargin, Derya Oliver, David K Lambe, Evelyn K |
author_facet | Sargin, Derya Oliver, David K Lambe, Evelyn K |
author_sort | Sargin, Derya |
collection | PubMed |
description | The activity of serotonin (5-HT) neurons is critical for mood regulation. In a mouse model of chronic social isolation, a known risk factor for depressive illness, we show that 5-HT neurons in the dorsal raphe nucleus are less responsive to stimulation. Probing the responsible cellular mechanisms pinpoints a disturbance in the expression and function of small-conductance Ca(2+)-activated K(+) (SK) channels and reveals an important role for both SK2 and SK3 channels in normal regulation of 5-HT neuronal excitability. Chronic social isolation renders 5-HT neurons insensitive to SK2 blockade, however inhibition of the upregulated SK3 channels restores normal excitability. In vivo, we demonstrate that inhibiting SK channels normalizes chronic social isolation-induced anxiety/depressive-like behaviors. Our experiments reveal a causal link for the first time between SK channel dysregulation and 5-HT neuron activity in a lifelong stress paradigm, suggesting these channels as targets for the development of novel therapies for mood disorders. DOI: http://dx.doi.org/10.7554/eLife.21416.001 |
format | Online Article Text |
id | pubmed-5119885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-51198852016-11-28 Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels Sargin, Derya Oliver, David K Lambe, Evelyn K eLife Neuroscience The activity of serotonin (5-HT) neurons is critical for mood regulation. In a mouse model of chronic social isolation, a known risk factor for depressive illness, we show that 5-HT neurons in the dorsal raphe nucleus are less responsive to stimulation. Probing the responsible cellular mechanisms pinpoints a disturbance in the expression and function of small-conductance Ca(2+)-activated K(+) (SK) channels and reveals an important role for both SK2 and SK3 channels in normal regulation of 5-HT neuronal excitability. Chronic social isolation renders 5-HT neurons insensitive to SK2 blockade, however inhibition of the upregulated SK3 channels restores normal excitability. In vivo, we demonstrate that inhibiting SK channels normalizes chronic social isolation-induced anxiety/depressive-like behaviors. Our experiments reveal a causal link for the first time between SK channel dysregulation and 5-HT neuron activity in a lifelong stress paradigm, suggesting these channels as targets for the development of novel therapies for mood disorders. DOI: http://dx.doi.org/10.7554/eLife.21416.001 eLife Sciences Publications, Ltd 2016-11-22 /pmc/articles/PMC5119885/ /pubmed/27874831 http://dx.doi.org/10.7554/eLife.21416 Text en © 2016, Sargin et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Sargin, Derya Oliver, David K Lambe, Evelyn K Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels |
title | Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels |
title_full | Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels |
title_fullStr | Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels |
title_full_unstemmed | Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels |
title_short | Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3 calcium-activated potassium channels |
title_sort | chronic social isolation reduces 5-ht neuronal activity via upregulated sk3 calcium-activated potassium channels |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119885/ https://www.ncbi.nlm.nih.gov/pubmed/27874831 http://dx.doi.org/10.7554/eLife.21416 |
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