Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation
Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. I...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-02-01
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| Online Access: | https://elifesciences.org/articles/99988 |
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| author | Mathias Guayasamin Lewis R Depaauw-Holt Ifeoluwa I Adedipe Ossama Ghenissa Juliette Vaugeois Manon Duquenne Benjamin Rogers Jade Latraverse-Arquilla Sarah Peyrard Anthony Bosson Ciaran Murphy-Royal |
| author_facet | Mathias Guayasamin Lewis R Depaauw-Holt Ifeoluwa I Adedipe Ossama Ghenissa Juliette Vaugeois Manon Duquenne Benjamin Rogers Jade Latraverse-Arquilla Sarah Peyrard Anthony Bosson Ciaran Murphy-Royal |
| author_sort | Mathias Guayasamin |
| collection | DOAJ |
| description | Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits. |
| format | Article |
| id | doaj-art-922606a2bf194b46b179432c7a83c02b |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-922606a2bf194b46b179432c7a83c02b2025-02-05T09:37:27ZengeLife Sciences Publications LtdeLife2050-084X2025-02-011310.7554/eLife.99988Early-life stress induces persistent astrocyte dysfunction associated with fear generalisationMathias Guayasamin0https://orcid.org/0009-0008-6099-930XLewis R Depaauw-Holt1https://orcid.org/0009-0001-3797-447XIfeoluwa I Adedipe2Ossama Ghenissa3Juliette Vaugeois4Manon Duquenne5Benjamin Rogers6Jade Latraverse-Arquilla7Sarah Peyrard8Anthony Bosson9Ciaran Murphy-Royal10https://orcid.org/0000-0001-7545-593XDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaCentre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaDépartement de Neurosciences, Université de Montréal, Montréal, Canada; Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, CanadaEarly-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits.https://elifesciences.org/articles/99988glial cellastrocytesearly-life stressengramlearning and memoryneuron–glia interactions |
| spellingShingle | Mathias Guayasamin Lewis R Depaauw-Holt Ifeoluwa I Adedipe Ossama Ghenissa Juliette Vaugeois Manon Duquenne Benjamin Rogers Jade Latraverse-Arquilla Sarah Peyrard Anthony Bosson Ciaran Murphy-Royal Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation eLife glial cell astrocytes early-life stress engram learning and memory neuron–glia interactions |
| title | Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation |
| title_full | Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation |
| title_fullStr | Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation |
| title_full_unstemmed | Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation |
| title_short | Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation |
| title_sort | early life stress induces persistent astrocyte dysfunction associated with fear generalisation |
| topic | glial cell astrocytes early-life stress engram learning and memory neuron–glia interactions |
| url | https://elifesciences.org/articles/99988 |
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