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

**Authors:** Ryo Egashira, Meng-Tsen Ke, Nao Nakagawa-Tamagawa, Satoshi Fujimoto, Shigenori Inagaki, Tsuyoshi Takagi, Tsuyoshi Miyakawa, Yoshiaki Tagawa, Takeshi Imai

PMC · DOI: 10.1126/sciadv.adw8458 · Science Advances · 2026-01-14

## TL;DR

This study shows that spine formation in specific parts of neurons during adolescence is crucial for brain development and cognitive maturation.

## Contribution

The study reveals experience-dependent spine formation in a specific dendritic compartment of L5 neurons during adolescence.

## Key findings

- Spine density increases in the middle compartment of apical dendrites during adolescence in a experience-dependent manner.
- Spine accumulation at the hotspot is impaired in mouse models of schizophrenia.
- Compartment-specific spine formation supports nonlinear dendritic integration and cognitive maturation.

## Abstract

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.

Mouse models of schizophrenia show defects in adolescent spine formation in a specific dendritic compartment of L5 neurons.

## Linked entities

- **Diseases:** schizophrenia (MONDO:0005090)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** neuropsychiatric disorders (MESH:D001523), schizophrenia (MESH:D012559)
- **Chemicals:** calcium (MESH:D002118)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12802838/full.md

## References

79 references — full list in the complete paper: https://tomesphere.com/paper/PMC12802838/full.md

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Source: https://tomesphere.com/paper/PMC12802838