Cargando…

GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo

Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elu...

Descripción completa

Detalles Bibliográficos
Autores principales: Moreno-Jiménez, E. P., Flor-García, M., Hernández-Vivanco, A., Terreros-Roncal, J., Rodríguez-Moreno, C. B., Toni, N., Méndez, P., Llorens-Martín, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363517/
https://www.ncbi.nlm.nih.gov/pubmed/37481766
http://dx.doi.org/10.1007/s00018-023-04874-w
_version_ 1785076644223909888
author Moreno-Jiménez, E. P.
Flor-García, M.
Hernández-Vivanco, A.
Terreros-Roncal, J.
Rodríguez-Moreno, C. B.
Toni, N.
Méndez, P.
Llorens-Martín, María
author_facet Moreno-Jiménez, E. P.
Flor-García, M.
Hernández-Vivanco, A.
Terreros-Roncal, J.
Rodríguez-Moreno, C. B.
Toni, N.
Méndez, P.
Llorens-Martín, María
author_sort Moreno-Jiménez, E. P.
collection PubMed
description Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3β) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3β-overexpressing newborn neurons show an increased number and altered size of Gephyrin(+) postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3β overexpression triggers a depletion of Parvalbumin(+) interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3β is dysregulated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-023-04874-w.
format Online
Article
Text
id pubmed-10363517
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-103635172023-07-25 GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo Moreno-Jiménez, E. P. Flor-García, M. Hernández-Vivanco, A. Terreros-Roncal, J. Rodríguez-Moreno, C. B. Toni, N. Méndez, P. Llorens-Martín, María Cell Mol Life Sci Original Article Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3β) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3β-overexpressing newborn neurons show an increased number and altered size of Gephyrin(+) postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3β overexpression triggers a depletion of Parvalbumin(+) interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3β is dysregulated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-023-04874-w. Springer International Publishing 2023-07-23 2023 /pmc/articles/PMC10363517/ /pubmed/37481766 http://dx.doi.org/10.1007/s00018-023-04874-w Text en © The Author(s) 2023 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 Original Article
Moreno-Jiménez, E. P.
Flor-García, M.
Hernández-Vivanco, A.
Terreros-Roncal, J.
Rodríguez-Moreno, C. B.
Toni, N.
Méndez, P.
Llorens-Martín, María
GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
title GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
title_full GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
title_fullStr GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
title_full_unstemmed GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
title_short GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
title_sort gsk-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363517/
https://www.ncbi.nlm.nih.gov/pubmed/37481766
http://dx.doi.org/10.1007/s00018-023-04874-w
work_keys_str_mv AT morenojimenezep gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT florgarciam gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT hernandezvivancoa gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT terrerosroncalj gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT rodriguezmorenocb gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT tonin gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT mendezp gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo
AT llorensmartinmaria gsk3borchestratestheinhibitoryinnervationofadultborndentategranulecellsinvivo