Scientists studying brain development at Kyushu University in Japan have uncovered a previously unrecognised pattern of neural connectivity that appears during adolescence and may influence both cognitive maturation and risk for neuropsychiatric conditions such as schizophrenia.
Traditional theories of adolescent brain development held that the primary process after childhood was synaptic pruning, where excess neuronal connections are removed. This pruning was long thought to shape the brain’s efficiency and, when excessive, to contribute to disorders like schizophrenia, which involves symptoms such as delusions and disorganised thinking.
In a study published in Science Advances on January 14, 2026, researchers used SeeDB2, a tissue‑clearing agent developed by the team, together with super‑resolution microscopy to make large sections of the mouse cerebral cortex transparent and map dendritic spines—the small protrusions on neurons where excitatory synapses form—across entire neurons in Layer 5 of the cortex for the first time. This layer integrates information from diverse sources and sends signals out of the cortex, making it central to complex brain functions.
The detailed mapping showed that, rather than being evenly distributed or only reduced by pruning, dendritic spines became highly concentrated in specific dendritic segments during adolescence, forming distinct “synapse hotspots.”In two‑week‑old mice, before adolescence, spine distribution was even; but between three and eight weeks of age—a period spanning early childhood to adolescence in mice—the density of spines rose sharply in a single region of the apical dendrite, giving rise to these hotspots.
To explore links with schizophrenia, the team studied mice engineered with mutations in genes associated with the disorder, including Setd1a, Hivep2, and Grin1. In these models, spine density appeared typical early in life, but during adolescence synapse formation was significantly reduced, preventing the usual emergence of hotspots. This suggests that failure to build new synaptic clusters during adolescence, not just excessive pruning, may be involved in the development of some schizophrenia‑related neural abnormalities.
Although the findings are currently limited to animal models and require further investigation to determine whether the same mechanisms apply to humans, they challenge long‑standing views of adolescent brain maturation and open new avenues for understanding how neural circuits supporting higher‑order thinking are constructed and how their disruption might relate to psychiatric disorders.
