Microglia shape the embryonic development of mammalian respiratory networks
Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled duri...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/80352 |
| _version_ | 1811323917628866560 |
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| author | Marie-Jeanne Cabirol Laura Cardoit Gilles Courtand Marie-Eve Mayeur John Simmers Olivier Pascual Muriel Thoby-Brisson |
| author_facet | Marie-Jeanne Cabirol Laura Cardoit Gilles Courtand Marie-Eve Mayeur John Simmers Olivier Pascual Muriel Thoby-Brisson |
| author_sort | Marie-Jeanne Cabirol |
| collection | DOAJ |
| description | Microglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Spi1+/+ (Pu.1 WT)) mouse (Mus musculus) brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBötzinger complex (preBötC)). In transgenic mice depleted of microglia (Spi1−/− (Pu.1 KO) mutant), we performed anatomical staining, calcium imaging, and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBötC at E16.5, and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBötC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Spi1−/− embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development. |
| first_indexed | 2024-04-13T14:05:02Z |
| format | Article |
| id | doaj.art-0ac07cd4a5b445f5b65d20ca09b1334a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-13T14:05:02Z |
| publishDate | 2022-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0ac07cd4a5b445f5b65d20ca09b1334a2022-12-22T02:43:56ZengeLife Sciences Publications LtdeLife2050-084X2022-11-011110.7554/eLife.80352Microglia shape the embryonic development of mammalian respiratory networksMarie-Jeanne Cabirol0Laura Cardoit1Gilles Courtand2Marie-Eve Mayeur3John Simmers4https://orcid.org/0000-0002-7487-4638Olivier Pascual5Muriel Thoby-Brisson6https://orcid.org/0000-0003-3214-1724Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS, Université de Bordeaux, Bordeaux, FranceInstitut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS, Université de Bordeaux, Bordeaux, FranceInstitut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS, Université de Bordeaux, Bordeaux, FranceMeLis INSERM U1314-CNRS UMR 5284, Faculté Rockefeller, Lyon, FranceInstitut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS, Université de Bordeaux, Bordeaux, FranceMeLis INSERM U1314-CNRS UMR 5284, Faculté Rockefeller, Lyon, FranceInstitut de Neurosciences Cognitives et Intégratives d’Aquitaine, CNRS, Université de Bordeaux, Bordeaux, FranceMicroglia, brain-resident macrophages, play key roles during prenatal development in defining neural circuitry function, including ensuring proper synaptic wiring and maintaining homeostasis. Mammalian breathing rhythmogenesis arises from interacting brainstem neural networks that are assembled during embryonic development, but the specific role of microglia in this process remains unknown. Here, we investigated the anatomical and functional consequences of respiratory circuit formation in the absence of microglia. We first established the normal distribution of microglia within the wild-type (WT, Spi1+/+ (Pu.1 WT)) mouse (Mus musculus) brainstem at embryonic ages when the respiratory networks are known to emerge (embryonic day (E) 14.5 for the parafacial respiratory group (epF) and E16.5 for the preBötzinger complex (preBötC)). In transgenic mice depleted of microglia (Spi1−/− (Pu.1 KO) mutant), we performed anatomical staining, calcium imaging, and electrophysiological recordings of neuronal activities in vitro to assess the status of these circuits at their respective times of functional emergence. Spontaneous respiratory-related activity recorded from reduced in vitro preparations showed an abnormally slow rhythm frequency expressed by the epF at E14.5, the preBötC at E16.5, and in the phrenic motor nerves from E16.5 onwards. These deficits were associated with a reduced number of active epF neurons, defects in commissural projections that couple the bilateral preBötC half-centers, and an accompanying decrease in their functional coordination. These abnormalities probably contribute to eventual neonatal death, since plethysmography revealed that E18.5 Spi1−/− embryos are unable to sustain breathing activity ex utero. Our results thus point to a crucial contribution of microglia in the proper establishment of the central respiratory command during embryonic development.https://elifesciences.org/articles/80352breathingdevelopmentmicroglianeural network |
| spellingShingle | Marie-Jeanne Cabirol Laura Cardoit Gilles Courtand Marie-Eve Mayeur John Simmers Olivier Pascual Muriel Thoby-Brisson Microglia shape the embryonic development of mammalian respiratory networks eLife breathing development microglia neural network |
| title | Microglia shape the embryonic development of mammalian respiratory networks |
| title_full | Microglia shape the embryonic development of mammalian respiratory networks |
| title_fullStr | Microglia shape the embryonic development of mammalian respiratory networks |
| title_full_unstemmed | Microglia shape the embryonic development of mammalian respiratory networks |
| title_short | Microglia shape the embryonic development of mammalian respiratory networks |
| title_sort | microglia shape the embryonic development of mammalian respiratory networks |
| topic | breathing development microglia neural network |
| url | https://elifesciences.org/articles/80352 |
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