Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments
Name:
41380_2018_226_MOESM1_ESM.docx
Size:
21.16Kb
Format:
Microsoft Word 2007
Description:
Supplemental files
Name:
41380_2018_226_MOESM2_ESM.docx
Size:
21.16Kb
Format:
Microsoft Word 2007
Description:
Supplemental files
Name:
41380_2018_226_MOESM3_ESM.docx
Size:
27.74Kb
Format:
Microsoft Word 2007
Description:
Supplemental files
Name:
41380_2018_226_MOESM4_ESM.docx
Size:
46.97Kb
Format:
Microsoft Word 2007
Description:
Supplemental files
Name:
41380_2018_226_MOESM5_ESM.docx
Size:
27.74Kb
Format:
Microsoft Word 2007
Description:
Supplemental files
Name:
41380_2018_226_MOESM6_ESM.docx
Size:
46.97Kb
Format:
Microsoft Word 2007
Description:
Supplemental files
Name:
41380_2018_226_MOESM7_ESM.tif
Size:
35.62Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM8_ESM.tif
Size:
38.20Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM9_ESM.tif
Size:
38.93Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM10_ESM.tif
Size:
36.01Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM11_ESM.tif
Size:
35.30Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM12_ESM.tif
Size:
34.99Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM13_ESM.tif
Size:
34.40Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM14_ESM.tif
Size:
29.40Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM15_ESM.tif
Size:
36.95Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM16_ESM.tif
Size:
32.46Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM17_ESM.tif
Size:
32.83Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM18_ESM.tif
Size:
33.39Mb
Format:
TIFF image
Description:
Supplemental files
Name:
41380_2018_226_MOESM19_ESM.tif
Size:
29.37Mb
Format:
TIFF image
Description:
Supplemental files
Type
ArticleAuthors
Petrelli, FrancescoDallérac, Glenn
Pucci, Luca
Cali, Corrado
Zehnder, Tamara
Sultan, Sébastien
Lecca, Salvatore
Chicca, Andrea
Ivanov, Andrei
Asensio, Cédric S.
Gundersen, Vidar
Toni, Nicolas
Knott, Graham William
Magara, Fulvio
Gertsch, Jürg
Kirchhoff, Frank
Déglon, Nicole
Giros, Bruno
Edwards, Robert H.
Mothet, Jean-Pierre
Bezzi, Paola
Date
2018-08-20Online Publication Date
2018-08-20Print Publication Date
2020-04Permanent link to this record
http://hdl.handle.net/10754/628466
Metadata
Show full item recordAbstract
Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders.Citation
Petrelli F, Dallérac G, Pucci L, Calì C, Zehnder T, et al. (2018) Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments. Molecular Psychiatry. Available: http://dx.doi.org/10.1038/s41380-018-0226-y.Sponsors
We would like to thank G. Carmignoto and C. Lüscher for their discussions and comments on the manuscript; K. Tan and M. Mameli for the in vivo electrophysiology of aVMAT2cKO mice; M. Rey and V. Zimmer for producing the lentivirus and performing the stereotactic surgery; C. Bellone and S. Bariselli for providing virus and advices for optogenetic experiments; the Division of Pharmacology and Toxicology and E. Grouzmann for quantifying brain monoamines; P. Fossier for sharing his electrophysiological equipment; J. Marchaland for her technical support; and J. Gremion for his help with the immunohistochemistry experiments. The study was supported by grants from the Swiss National Foundation NCCR 'Synapsy' (51NF40-158776) and 'Transcure' (51NF40-160620) to PB, operating grants from the Agence National de la Recherche (ANR-09-MNPS-022-01), Fondation pour la Recherche Médicale (Equipe FRM DEQ20150331734), CNRS, Université Aix-Marseille and Conseil Régional Provence Alpes Côte d'Azur to JPM, and NSERC RGPIN grant 385732-2012 to B.G.Publisher
Springer NatureJournal
Molecular PsychiatryAdditional Links
https://www.nature.com/articles/s41380-018-0226-yae974a485f413a2113503eed53cd6c53
10.1038/s41380-018-0226-y
Scopus Count
Except where otherwise noted, this item's license is described as 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/.