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Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila
The emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514485/ https://www.ncbi.nlm.nih.gov/pubmed/34645891 http://dx.doi.org/10.1038/s41598-021-99868-8 |
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author | Giachello, Carlo N. G. Fan, Yuen Ngan Landgraf, Matthias Baines, Richard A. |
author_facet | Giachello, Carlo N. G. Fan, Yuen Ngan Landgraf, Matthias Baines, Richard A. |
author_sort | Giachello, Carlo N. G. |
collection | PubMed |
description | The emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are not well understood. In particular, the mechanisms that transduce neuronal activity to regulating changes in neuronal physiology or structure are not known. Here, we take advantage of a recently identified invertebrate model for studying critical periods, the Drosophila larval locomotor system. Manipulation of neuronal activity during this critical period is sufficient to increase synaptic excitation and to permanently leave the locomotor network prone to induced seizures. Using genetics and pharmacological manipulations, we identify nitric oxide (NO)-signaling as a key mediator of activity. Transiently increasing or decreasing NO-signaling during the critical period mimics the effects of activity manipulations, causing the same lasting changes in synaptic transmission and susceptibility to seizure induction. Moreover, the effects of increased activity on the developing network are suppressed by concomitant reduction in NO-signaling and enhanced by additional NO-signaling. These data identify NO signaling as a downstream effector, providing new mechanistic insight into how activity during a critical period tunes a developing network. |
format | Online Article Text |
id | pubmed-8514485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85144852021-10-14 Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila Giachello, Carlo N. G. Fan, Yuen Ngan Landgraf, Matthias Baines, Richard A. Sci Rep Article The emergence of coordinated network function during nervous system development is often associated with critical periods. These phases are sensitive to activity perturbations during, but not outside, of the critical period, that can lead to permanently altered network function for reasons that are not well understood. In particular, the mechanisms that transduce neuronal activity to regulating changes in neuronal physiology or structure are not known. Here, we take advantage of a recently identified invertebrate model for studying critical periods, the Drosophila larval locomotor system. Manipulation of neuronal activity during this critical period is sufficient to increase synaptic excitation and to permanently leave the locomotor network prone to induced seizures. Using genetics and pharmacological manipulations, we identify nitric oxide (NO)-signaling as a key mediator of activity. Transiently increasing or decreasing NO-signaling during the critical period mimics the effects of activity manipulations, causing the same lasting changes in synaptic transmission and susceptibility to seizure induction. Moreover, the effects of increased activity on the developing network are suppressed by concomitant reduction in NO-signaling and enhanced by additional NO-signaling. These data identify NO signaling as a downstream effector, providing new mechanistic insight into how activity during a critical period tunes a developing network. Nature Publishing Group UK 2021-10-13 /pmc/articles/PMC8514485/ /pubmed/34645891 http://dx.doi.org/10.1038/s41598-021-99868-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Giachello, Carlo N. G. Fan, Yuen Ngan Landgraf, Matthias Baines, Richard A. Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila |
title | Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila |
title_full | Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila |
title_fullStr | Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila |
title_full_unstemmed | Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila |
title_short | Nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in Drosophila |
title_sort | nitric oxide mediates activity-dependent change to synaptic excitation during a critical period in drosophila |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514485/ https://www.ncbi.nlm.nih.gov/pubmed/34645891 http://dx.doi.org/10.1038/s41598-021-99868-8 |
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