Prenatal assembly of functional cortical circuits

Abstract The extent to which early brain maturation requires interactions with the outside world is a central question in neurobiology. Because much of cortical maturation occurs after birth in Mus , it has often been viewed as dependent on postnatal experience. However, studies addressing this issue have largely relied on postnatal sensory deprivation paradigms, which perturb normal development and cannot determine to what extent postnatal experience per se drives maturation. To address this question, here we compare two related rodents with markedly different gestation lengths: the precocial Acomys dimidiatus (39-day gestation) and the altricial Mus musculus (19-day gestation). By generating a novel Acomys reference genome and using histology, cellular birth dating, electrophysiology, single-nucleus transcriptomics, and quantitative behavior, we show that Acomys preserves the canonical sequence and timing of cortical development, while shifting major milestones of neuronal, circuit and behavioral maturation into prenatal life. At birth, Acomys cortex already shows advanced cytoarchitecture, neuronal physiology, thalamocortical barrels, transcriptional states, and sensorimotor behavior, with postnatal molecular programs in Mus unfolding prenatally in Acomys . Thus, birth is not a prerequisite for early cortical maturation. Instead, evolutionarily conserved developmental programs unfold across birth, with birth occurring at different stages of these programs, reflecting a species-specific balance between neonatal competence and prolonged postnatal plasticity.