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Plasticity of thalamocortical axons is regulated by serotonin levels modulated by preterm birth

Alexander Sinclair-Wilson, Akindé Lawrence, Isabelle Ferezou, Hugues Cartonnet, Caroline Mailhes, Sonia Garel#, Ludmilla Lokmane#


Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.

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Proc Natl Acad Sci USA. 2023 Aug 15 ; 120(33):e2301644120. doi:10.1073/pnas.2301644120