A disynaptic trigeminal circuit for the transformation and integration of oral chemesthesis in male mice
5 affiliations
- 1Flavour Science Research Center, College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
- 2Flavour Science Laboratory, Beijing Life Science Academy (BLSA), Beijing 102209, China.
- 3State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
- 4State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
- 5University of Chinese Academy of Sciences, Beijing 100101, China.
Abstract
Chemesthesis, encompassing oral sensations such as spiciness and coolness, is an important yet incompletely understood component of mammalian chemical sensing. Unlike taste or olfaction, these sensations are conveyed primarily through trigeminal pathways; however, how modality-specific peripheral signals are processed and transformed along central ascending pathways remains poorly understood. Herein, we delineate the structural and functional organization of an ascending trigeminal-brainstem-parabrachial circuit that mediates oral chemesthetic processing in male mice. Using viral tracing, in vivo calcium imaging, and chemogenetic and optogenetic manipulations, we identify a genetically defined disynaptic glutamatergic pathway (trigeminal ganglion → spinal trigeminal nucleus caudalis → lateral parabrachial nucleus) that is both necessary and sufficient for capsaicin- and menthol-evoked defensive behaviors. Although peripheral TRPV1+ and TRPM8+ neurons retain a degree of modality bias, we observe substantial convergence of spicy and cooling signals within the spinal trigeminal nucleus, followed by sustained and synchronized population activity in vglut2+ neurons of the external lateral parabrachial nucleus. This hierarchical transformation from peripheral segregation to central integration reveals the organizational principle by which distinct chemesthetic modalities are progressively integrated along a trigeminal-mediated ascending pathway, providing a circuit-level framework for understanding how chemical stimuli are processed and coordinated to drive defensive behaviors.
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BibTeX
@article{liu2026disynaptic,
title = {{A disynaptic trigeminal circuit for the transformation and integration of oral chemesthesis in male mice}},
author = {Fuqiang Liu and Kun Cui and Jian Mao and Hanyu Wang and Boyang Li and Lulu Guo and Na Zhang and Ying Li and Sisi Ruan and Wenhao Pei and Zhilin Hao and Qidong Zhang and Guobi Chai and Chang Liu and Chen Zhang and Jingrong Wang and Sensen Zhang and Long Li and Yun-Feng Zhang and Jianping Xie},
journal = {Science Advances},
year = {2026},
month = nov,
doi = {10.1126/sciadv.aeh5390},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aeh5390},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - A disynaptic trigeminal circuit for the transformation and integration of oral chemesthesis in male mice
AU - Fuqiang Liu
AU - Kun Cui
AU - Jian Mao
AU - Hanyu Wang
AU - Boyang Li
AU - Lulu Guo
AU - Na Zhang
AU - Ying Li
AU - Sisi Ruan
AU - Wenhao Pei
AU - Zhilin Hao
AU - Qidong Zhang
AU - Guobi Chai
AU - Chang Liu
AU - Chen Zhang
AU - Jingrong Wang
AU - Sensen Zhang
AU - Long Li
AU - Yun-Feng Zhang
AU - Jianping Xie
PY - 2026
DA - 2026/11/04
JO - Science Advances
DO - 10.1126/sciadv.aeh5390
UR - https://www.science.org/doi/abs/10.1126/sciadv.aeh5390
AB - Chemesthesis, encompassing oral sensations such as spiciness and coolness, is an important yet incompletely understood component of mammalian chemical sensing. Unlike taste or olfaction, these sensations are conveyed primarily through trigeminal pathways; however, how modality-specific peripheral signals are processed and transformed along central ascending pathways remains poorly understood. Herein, we delineate the structural and functional organization of an ascending trigeminal-brainstem-parabrachial circuit that mediates oral chemesthetic processing in male mice. Using viral tracing, in vivo calcium imaging, and chemogenetic and optogenetic manipulations, we identify a genetically defined disynaptic glutamatergic pathway (trigeminal ganglion → spinal trigeminal nucleus caudalis → lateral parabrachial nucleus) that is both necessary and sufficient for capsaicin- and menthol-evoked defensive behaviors. Although peripheral TRPV1+ and TRPM8+ neurons retain a degree of modality bias, we observe substantial convergence of spicy and cooling signals within the spinal trigeminal nucleus, followed by sustained and synchronized population activity in vglut2+ neurons of the external lateral parabrachial nucleus. This hierarchical transformation from peripheral segregation to central integration reveals the organizational principle by which distinct chemesthetic modalities are progressively integrated along a trigeminal-mediated ascending pathway, providing a circuit-level framework for understanding how chemical stimuli are processed and coordinated to drive defensive behaviors.
SN - 2375-2548
ER -