Dendritic compartment-specific spine formation in layer 5 neurons underlies cortical circuit maturation during adolescence.

The development of cognitive functions continues into adolescence. However, it is not fully understood how cortical circuitry changes during adolescence. Here, we performed a comprehensive super-resolution mapping of dendritic spines in layer 5 extratelencepharic-projecting (L5 ET) neurons in the primary somatosensory cortex in mice. In adults, the dendritic spines are highly enriched in the middle compartment of the apical dendrites (spine density "hotspot"), where dendritic calcium spikes are generated. In early development, dendritic spines are evenly distributed. During adolescence, however, the spine density increases specifically in the middle compartment of the apical dendrites in an experience-dependent manner, while other dendritic compartments show a slight reduction. Furthermore, spine accumulation at the hotspot was specifically impaired in mouse models of schizophrenia, demonstrating a link between adolescent spine formation and neuropsychiatric disorders. Our finding suggests that the dendritic compartment-specific spine formation during adolescence shapes nonlinear dendritic integration in L5 ET neurons and supports the maturation of cognitive functions.