Selective vulnerability of intracortical projection neurons drives long-term cortical circuit rewiring after perinatal hypoxia
Abstract
Cortical circuits are built at perinatal times and gradually refined in an activity-dependent manner during a so-called postnatal period of critical plasticity. Although lesions of the central nervous system (CNS) happening during this period typically recover better than those occurring later in life, they are often associated with long-term behavioral deficits. This suggests that neuronal circuits rewiring, in particular within the cortex, may either be incomplete or inappropriate.
To address this possibility, we used chronic perinatal hypoxia, a mouse model of very premature birth. We confirmed that chronic hypoxia induced a decrease in cortical thickness frequently observed in very preterm babies, which rapidly recovered 8 days later. To explore the transcriptional correlates of this recovery we next performed singlenuclei transcriptomic analysis of the cortex at short (P11) and long (P45) timepoints following hypoxia. This revealed persistent transcriptional changes within neurons, including of genes involved in mitochondrial metabolism, axonogenesis and synaptogenesis. Further, histological analysis using anterograde and retrograde tracing as well as mitochondrial labelling support persistent alterations in upper cortical neurons resulting in increased corticocortical connectivity within the cortex of adult hypoxic mice. Finally, behavioral testing revealed altered social behavior in mice exposed to chronic hypoxia, which amplified with age.
Altogether, our results unravel how brain lesions happening early in life, alter normal cortical development and have long term consequences on cortical wiring, contributing to the observed behaviors defects appearing later in life.
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BibTeX
@misc{ellouze2026selective,
title = {{Selective vulnerability of intracortical projection neurons drives long-term cortical circuit rewiring after perinatal hypoxia}},
author = {Salma Ellouze and Elodie Babina and Géraldine Meyer-Dilhet and Louis Foucault and Amel Amara and Stevenson Desmercière and Thomas Gagnieu and Sandrine Mongellaz and Anis Cataldi and Guillaume Marcy and Jean Francois Ghersi-Egea and Julien Courchet and Olivier Raineteau},
howpublished = {HAL},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753115},
url = {https://hal.science/hal-05791015v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Selective vulnerability of intracortical projection neurons drives long-term cortical circuit rewiring after perinatal hypoxia
AU - Salma Ellouze
AU - Elodie Babina
AU - Géraldine Meyer-Dilhet
AU - Louis Foucault
AU - Amel Amara
AU - Stevenson Desmercière
AU - Thomas Gagnieu
AU - Sandrine Mongellaz
AU - Anis Cataldi
AU - Guillaume Marcy
AU - Jean Francois Ghersi-Egea
AU - Julien Courchet
AU - Olivier Raineteau
PY - 2026
DA - 2026/09/21
PB - HAL
DO - 10.64898/2026.09.21.753115
UR - https://hal.science/hal-05791015v1
AB - Cortical circuits are built at perinatal times and gradually refined in an activity-dependent manner during a so-called postnatal period of critical plasticity. Although lesions of the central nervous system (CNS) happening during this period typically recover better than those occurring later in life, they are often associated with long-term behavioral deficits. This suggests that neuronal circuits rewiring, in particular within the cortex, may either be incomplete or inappropriate. To address this possibility, we used chronic perinatal hypoxia, a mouse model of very premature birth. We confirmed that chronic hypoxia induced a decrease in cortical thickness frequently observed in very preterm babies, which rapidly recovered 8 days later. To explore the transcriptional correlates of this recovery we next performed singlenuclei transcriptomic analysis of the cortex at short (P11) and long (P45) timepoints following hypoxia. This revealed persistent transcriptional changes within neurons, including of genes involved in mitochondrial metabolism, axonogenesis and synaptogenesis. Further, histological analysis using anterograde and retrograde tracing as well as mitochondrial labelling support persistent alterations in upper cortical neurons resulting in increased corticocortical connectivity within the cortex of adult hypoxic mice. Finally, behavioral testing revealed altered social behavior in mice exposed to chronic hypoxia, which amplified with age. Altogether, our results unravel how brain lesions happening early in life, alter normal cortical development and have long term consequences on cortical wiring, contributing to the observed behaviors defects appearing later in life.
ER -