A disynaptic trigeminal circuit for the transformation and integration of oral chemesthesis in male mice.

A genetically defined disynaptic glutamatergic trigeminal pathway (trigeminal ganglion → spinal trigeminal nucleus caudalis → lateral parabrachial nucleus) is necessary and sufficient for capsaicin- and menthol-evoked defensive behaviors in male mice.

• Why it matters: Oral chemesthesis is conveyed mainly via trigeminal pathways, but the circuit-level transformation and integration of modality-specific peripheral signals along ascending routes is unclear.
• What they did: In male mice, viral tracing, in vivo calcium imaging, and chemogenetic/optogenetic perturbations mapped and tested an ascending trigeminal-brainstem-parabrachial circuit, including vglut2+ activity in the external lateral parabrachial nucleus.
• The result: Peripheral TRPV1+ and TRPM8+ neurons show modality bias, yet spicy and cooling inputs converge in the spinal trigeminal nucleus and produce sustained, synchronized vglut2+ population activity, supporting a hierarchical integration framework for defensive responses.

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