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bioRxiv · 10.1101/2022.06.24.497556

Diverse thermosensory receptors and neurons mediate the neural coding of oral cooling in the mouse trigeminothalamic tract

Li, J.·Lemon, C. H.
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Abstract

Different sets of peripheral and medullary trigeminal neurons respond across a cooling gradient applied to intraoral skin. Here we applied electrophysiology to anesthetized mice to study if different types of cool-driven trigeminothalamic neurons convey oral cooling information to the thalamus. We monitored spiking responses to oral stimulation with cold ([≤]13{degrees}C), cool (21{degrees}C to 28{degrees}C), neutral (35{degrees}C), and warm/hot ([≥]40{degrees}C) water in single trigeminal nucleus caudalis (Vc) neurons physiologically tested for projections to the thalamus. We also recorded oral thermal responses from Vc neurons in mice gene deficient for the cooling and menthol receptor TRPM8 to study afferent mechanisms of central oral thermosensory activity. We found that thalamic-projecting Vc neurons that respond to oral cooling comprise heterogeneous cell types. These cell types showed unique temporal response kinetics across cool and cold temperatures, with tuning to select ranges of a cooling gradient. The combined thermal activity of multiple, differently tuned types of trigeminothalamic cooling neurons offered greater contrast between cold, cool, and warm temperatures in multivariate analysis than the responses of the individual neural types alone, agreeing with a neural population code for cooling information. Compared to control, TRPM8 deficient mice demonstrated a loss of Vc neurons tuned to mild oral cooling, but maintained Vc cells responsive to intense cold. Notably, distinctions between Vc population responses to mild cool and warm temperatures were impaired in TRPM8 deficient mice, suggesting a role for TRPM8 in oral warmth recognition. Diverse receptors and neurons mediate oral cooling signals carried by the trigeminothalamic pathway.

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Li, J., Lemon, C. H.. 2022-06-27. Diverse thermosensory receptors and neurons mediate the neural coding of oral cooling in the mouse trigeminothalamic tract. https://doi.org/10.1101/2022.06.24.497556

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