BEYOND HUMAN BRADYCHRONY: SPECIES-DIVERGENT DENDRITIC MATURATION AND SYNAPTIC FUNCTION IN GREAT APE INEURONS

On a macroscopic level, human neurodevelopment is marked by increased neurogenesis and prolonged neuronal maturation compared to great apes, and seminal genetics-first studies have implicated multiple human-specific genomic events in this contrast. Yet, a critical aspect of extended development remains underexplored: how dendrites implement signal integration over time, and whether species differences reflect purely bradychronic delays or also qualitatively distinct integration regimes, a distinction with major computational consequences.
We address this by profiling key determinants of dendritic integration across development in iPSC-derived glutamatergic iNeurons from human and other great apes (chimpanzee, bonobo). We integrate dendritic reconstructions, synapse imaging, and immunocytochemical readouts of major voltage-gated conductance families (sodium/potassium/HCN/calcium), and apply morphology-aware mapping to project signal densities and synapse puncta onto dendritic segments to derive morphology-conditioned profiles (e.g., puncta density versus distance from soma). In parallel, miniature excitatory postsynaptic current (mEPSC) recordings track synaptic functional maturation.
Across development, dendritic architecture exhibits species-divergent trajectories that extend beyond a single bradychrony axis, motivating a compartment-resolved view of maturation. Determinants of integration follow a mixed pattern: some are consistent with bradychronic timing, while others show species-specific compartmental tuning, indicating that ‘slower’ and ‘different’ can coexist within the same cell. These findings suggest that human neurons may undergo distinct developmental tuning, with dendritic processing regimes that uniquely shape human information flow and learning rules.