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Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons
During development, newly-differentiated neurons undergo several morphological and physiological changes to become functional, mature neurons. Physiologic maturation of neuronal cells derived from isolated stem or progenitor cells may provide insight into maturation in vivo but is not well studied....
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012889/ https://www.ncbi.nlm.nih.gov/pubmed/32047174 http://dx.doi.org/10.1038/s41598-020-58120-5 |
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author | Venugopalan, Praseeda Cameron, Evan G. Zhang, Xiong Nahmou, Michael Muller, Kenneth J. Goldberg, Jeffrey L. |
author_facet | Venugopalan, Praseeda Cameron, Evan G. Zhang, Xiong Nahmou, Michael Muller, Kenneth J. Goldberg, Jeffrey L. |
author_sort | Venugopalan, Praseeda |
collection | PubMed |
description | During development, newly-differentiated neurons undergo several morphological and physiological changes to become functional, mature neurons. Physiologic maturation of neuronal cells derived from isolated stem or progenitor cells may provide insight into maturation in vivo but is not well studied. As a step towards understanding how neuronal maturation is regulated, we studied the developmental switch of response to the neurotransmitter GABA, from excitatory depolarization to inhibitory hyperpolarization. We compared acutely isolated retinal ganglion cells (RGCs) at various developmental stages and RGCs differentiated in vitro from embryonic retinal progenitors for the effects of aging and, independently, of retinal environment age on their GABA(A) receptor (GABA(A)R) responses, elicited by muscimol. We found that neurons generated in vitro from progenitors exhibited depolarizing, immature GABA responses, like those of early postnatal RGCs. As progenitor-derived neurons aged from 1 to 3 weeks, their GABA responses matured. Interestingly, signals secreted by the early postnatal retina suppressed acquisition of mature GABA responses. This suppression was not associated with changes in expression of GABA(A)R or of the chloride co-transporter KCC2, but rather with inhibition of KCC2 dimerization in differentiating neurons. Taken together, these data indicate GABA response maturation depends on release of inhibition by developmentally regulated diffusible signals from the retina. |
format | Online Article Text |
id | pubmed-7012889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-70128892020-02-21 Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons Venugopalan, Praseeda Cameron, Evan G. Zhang, Xiong Nahmou, Michael Muller, Kenneth J. Goldberg, Jeffrey L. Sci Rep Article During development, newly-differentiated neurons undergo several morphological and physiological changes to become functional, mature neurons. Physiologic maturation of neuronal cells derived from isolated stem or progenitor cells may provide insight into maturation in vivo but is not well studied. As a step towards understanding how neuronal maturation is regulated, we studied the developmental switch of response to the neurotransmitter GABA, from excitatory depolarization to inhibitory hyperpolarization. We compared acutely isolated retinal ganglion cells (RGCs) at various developmental stages and RGCs differentiated in vitro from embryonic retinal progenitors for the effects of aging and, independently, of retinal environment age on their GABA(A) receptor (GABA(A)R) responses, elicited by muscimol. We found that neurons generated in vitro from progenitors exhibited depolarizing, immature GABA responses, like those of early postnatal RGCs. As progenitor-derived neurons aged from 1 to 3 weeks, their GABA responses matured. Interestingly, signals secreted by the early postnatal retina suppressed acquisition of mature GABA responses. This suppression was not associated with changes in expression of GABA(A)R or of the chloride co-transporter KCC2, but rather with inhibition of KCC2 dimerization in differentiating neurons. Taken together, these data indicate GABA response maturation depends on release of inhibition by developmentally regulated diffusible signals from the retina. Nature Publishing Group UK 2020-02-11 /pmc/articles/PMC7012889/ /pubmed/32047174 http://dx.doi.org/10.1038/s41598-020-58120-5 Text en © The Author(s) 2020 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 Venugopalan, Praseeda Cameron, Evan G. Zhang, Xiong Nahmou, Michael Muller, Kenneth J. Goldberg, Jeffrey L. Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
title | Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
title_full | Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
title_fullStr | Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
title_full_unstemmed | Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
title_short | Physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
title_sort | physiologic maturation is both extrinsically and intrinsically regulated in progenitor-derived neurons |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012889/ https://www.ncbi.nlm.nih.gov/pubmed/32047174 http://dx.doi.org/10.1038/s41598-020-58120-5 |
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