Linhui Zhu1,2,3,4 · Huitaong Hong2,3,4 · Mengyi Qian5  · Wang Cao2,3,4 · Zirui Luo2,3,4 · Jianke Gong1  · Wenjuan Zou5  · Lijun Kang2,3,4

1 College of Life Science and Technology, Key Laboratory of Molecular Biophysics of MOE, Huazhong University of Science and Technology, Wuhan 430074, China 

2 Department of Neurology of the Fourth Affiliated Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Yiwu 322000, China 

3 NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou 310053, China 

4 Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain‑machine Integration, State Key Laboratory of Brain‑machine Intelligence, Zhejiang University, Hangzhou 311121, China 

5 Department of Neurosurgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

Abstract

Polymodal sensory neurons integrate diverse stimuli for environmental perception, but their modality discrimination mechanisms remain unclear. We focused on Caenorhabditis elegans inner labial type 1 (IL1) neurons, key polymodal neurons mediating mechanical and cold responses, and identified a hierarchical channel system supporting their multimodal function. Specifically, DEG-1 sodium channels are dedicated mechanotransduction receptors; GLR-3 glutamate receptors are the main rapid cold sensors, driving cold-induced calcium signals and behaviors; TRPA-1 bidirectionally modulates mechanical adaptation via calcium signaling and promotes cold-related longevity. This framework reveals a polymodal design logic: dedicated channels (DEG-1/GLR-3) process discrete modalities in parallel for specificity, while TRPA-1 regulates both. Our work provides a molecular blueprint for IL1’s precise stimulus processing, offering insights into conserved multimodal integration mechanisms across lineages.

Keywords

Polymodal sensation; Mechanosensation; Thermosensation; Mechano-gated channel; Cold receptor; TRP channel

[SpringerLink]