A subtype-specific gene regulatory program controls differential circuit integration of deep CA3 pyramidal neurons

Postnatal loss of ST18 in deep CA3 pyramidal neurons shifts their transcriptional and chromatin state toward a superficial-like program, coinciding with near-superficial thorny excrescence elaboration.

• Why it matters: Deep and superficial CA3 subtypes integrate into different circuits, but the molecular rules that restrict alternative subtype programs during postnatal maturation are unclear.
• What they did: Using developmental single-nucleus multiomics with genetic targeting, morphological profiling, and electrophysiology, the study identifies ST18 as a regulator of deep CA3 identity and predicts it represses a superficial-associated program.
• The result: ST18 loss increases TE elaboration, enhances excitatory synaptic activity, and reduces burst-firing, linking subtype-specific gene regulation to differential circuit integration in CA3.

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