Developmental Trajectory of Synaptic Remodeling in the Mouse Prefrontal Cortex

The prefrontal cortex (PFC) is a heteromodal association area critical for higher-order cognitive functions. Its protracted maturation extends through adolescence into early adulthood, a period characterized by extensive remodeling of neuronal networks and synaptic architecture. This heightened plasticity supports the refinement of prefrontal circuits necessary to meet the evolving cognitive and behavioral demands of this developmental transition. However, the extended maturation window also increases vulnerability to environmental perturbations, which can lead to lasting synaptic and cognitive impairments. Despite widespread use of developmental disruption models during adolescence, a systematic characterization of synaptic dynamics during normal PFC maturation is lacking. Here, we combined longitudinal in vivo two-photon imaging of dendritic spines with cross-sectional quantification of excitatory and inhibitory synapses, and microglia-mediated synaptic engulfment, in mice from juvenile to adult stages. This integrated approach provides a comprehensive reference atlas of normal prefrontal synaptic maturation, offering a framework for interpreting alterations to synapses in models of developmental disturbance.