Roig-Puiggros, S. | Search bioRxiv

bioRxiv2026

Prenatal assembly of functional cortical circuits

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.

neuroscience↗

bioRxiv2024

Emergence of neocortical function in heterotopic neurons

Brains come in various sizes and shapes, yet how neuronal position constrains the type of circuits that they can form remains largely unknown. The spatial layout of anatomical structures with corresponding functions varies widely across species (J-4). Also, during evolution, anatomical structures have duplicated and then diverged to generate new circuits and functions (5, 6). Thus, it is critical to understand how the position of neurons constrains their integration into circuits and, ultimately, their function. To address this question, we studied EmlJ knockout mice in which subsets of neocortical neurons form a new structure below the neocortex termed heterotopia (Ht). We examined how this new location affects the molecular identity, topography, input-output circuit connectivity, electrophysiology, and functional properties of these neurons. Our results reveal a striking conservation of the cellular features and circuit properties of Ht neurons, despite their abnormal location and misorientation. Supporting this observation, these neurons were able to functionally substitute for overlying neocortical neurons in a behaviorally relevant task when the latter were optogenetically silenced. Hence, specific neuronal identities and associated function can be reproduced in altered anatomical settings, revealing a remarkable level of self-organization and adaptability of neocortical circuits.

neuroscience↗