Human neurons undergo protracted functional maturation into adulthood

Human cognitive development is uniquely prolonged, reflecting the extended postnatal maturation of the cerebral cortex where cell-type differentiation, synaptogenesis, myelination and transcriptional regulation all follow protracted developmental timelines. However, when the intrinsic physiological properties of human cortical neurons mature, and how this compares with other species, remains unknown. Here we show, through patch-clamp recordings of temporal cortex from an ancestrally diverse cohort spanning infancy to adulthood, that human supragranular pyramidal neurons exhibit pronounced neoteny of their functional properties, maturing well into adult life. In the mouse the same sequence of changes unfolds within weeks and scales tightly with brain volume. In humans this allometric relationship is fundamentally different, with the trajectories of individual properties continuing for decades beyond peak brain volume, up to 7 times more slowly than the difference in brain growth rates alone would predict. Together, these trajectories define a continuous developmental axis along which the neuronal population progresses throughout cognitive development, with the neurons present at each stage differing in how they transform their inputs. Notably, the population diverges only in adolescence, when one of its two adult end-states acquires a distinctive physiology, absent in mice, that characterises the deep supragranular neurons linking distant cortical areas in humans and other primates. A generative model of the developing human supragranular population, unifying the developmental models of every physiological domain, now captures this protracted maturation from infancy to adulthood, providing a resource for simulation, normative referencing and cross-species age mapping.