Position-independent emergence of neocortical neuron molecular identity, connectivity and function

Brain architectures vary widely across species, yet how neuronal positioning constrains the type of circuits that can be made, and their function, remains poorly understood. Here we examine how neuronal position affects molecular identity, connectivity and function by studying Eml1 knockout mice, which exhibit abnormally located (heterotopic) neurons beneath the cortex. Heterotopic neurons maintained their molecular signatures, formed appropriate long-range connections and exhibited normal electrophysiological properties. They organized into functional sensory-processing centers that mirrored their cortical counterparts, with preserved somatotopic mapping and responsiveness to sensory stimuli. Remarkably, cortical silencing did not impair sensory discrimination, revealing that heterotopic neurons were the main drivers of this function. Hence, equivalent circuits can emerge in different spatial configurations, allowing diverse brain architectures to converge on similar functional outcomes. Overall design: Mouse single-nucleus RNA seq of FAC-sorted P23 SSp cells of Eml1lox/lox and Emx1:Cre; Eml1lox/lox