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Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2
The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTO...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328766/ https://www.ncbi.nlm.nih.gov/pubmed/35881440 http://dx.doi.org/10.7554/eLife.75398 |
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author | Kosillo, Polina Ahmed, Kamran M Aisenberg, Erin E Karalis, Vasiliki Roberts, Bradley M Cragg, Stephanie J Bateup, Helen S |
author_facet | Kosillo, Polina Ahmed, Kamran M Aisenberg, Erin E Karalis, Vasiliki Roberts, Bradley M Cragg, Stephanie J Bateup, Helen S |
author_sort | Kosillo, Polina |
collection | PubMed |
description | The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties, and whether they have similar or distinct functions is unknown. Here, we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. Disruption of both mTOR complexes leads to pronounced deficits in dopamine release demonstrating the importance of balanced mTORC1 and mTORC2 signaling for dopaminergic function. |
format | Online Article Text |
id | pubmed-9328766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-93287662022-07-28 Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 Kosillo, Polina Ahmed, Kamran M Aisenberg, Erin E Karalis, Vasiliki Roberts, Bradley M Cragg, Stephanie J Bateup, Helen S eLife Neuroscience The mTOR pathway is an essential regulator of cell growth and metabolism. Midbrain dopamine neurons are particularly sensitive to mTOR signaling status as activation or inhibition of mTOR alters their morphology and physiology. mTOR exists in two distinct multiprotein complexes termed mTORC1 and mTORC2. How each of these complexes affect dopamine neuron properties, and whether they have similar or distinct functions is unknown. Here, we investigated this in mice with dopamine neuron-specific deletion of Rptor or Rictor, which encode obligatory components of mTORC1 or mTORC2, respectively. We find that inhibition of mTORC1 strongly and broadly impacts dopamine neuron structure and function causing somatodendritic and axonal hypotrophy, increased intrinsic excitability, decreased dopamine production, and impaired dopamine release. In contrast, inhibition of mTORC2 has more subtle effects, with selective alterations to the output of ventral tegmental area dopamine neurons. Disruption of both mTOR complexes leads to pronounced deficits in dopamine release demonstrating the importance of balanced mTORC1 and mTORC2 signaling for dopaminergic function. eLife Sciences Publications, Ltd 2022-07-26 /pmc/articles/PMC9328766/ /pubmed/35881440 http://dx.doi.org/10.7554/eLife.75398 Text en © 2022, Kosillo, Ahmed et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Kosillo, Polina Ahmed, Kamran M Aisenberg, Erin E Karalis, Vasiliki Roberts, Bradley M Cragg, Stephanie J Bateup, Helen S Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 |
title | Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 |
title_full | Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 |
title_fullStr | Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 |
title_full_unstemmed | Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 |
title_short | Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2 |
title_sort | dopamine neuron morphology and output are differentially controlled by mtorc1 and mtorc2 |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9328766/ https://www.ncbi.nlm.nih.gov/pubmed/35881440 http://dx.doi.org/10.7554/eLife.75398 |
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