Diversity in the Neural Circuitry of Cold Sensing Revealed by Genetic Axonal Labeling of Transient Receptor Potential Melastatin 8 Neurons

• DOI: 10.1523/jneurosci.4578-07.2007
• Publication Date: 2007-12-19T18:53:08Z
• Authors: Yoshio Takashima; Richard L. Daniels; Wendy Knowlton; James Teng; Emily R. Liman; David D. McKemy
• Keywords: TRPM8; Nociceptor; Thermoreceptor; Cold sensitivity

Sensory nerves detect an extensive array of somatosensory stimuli, including environmental temperatures. Despite activating only a small cohort sensory neurons, cold temperatures generate variety distinct sensations that range from pleasantly cool to painfully aching, prickling, and burning. Psychophysical functional data show responses are mediated by both C- Aδ-fibers with separate peripheral receptive zones, each which likely provides one or more these sensations. With this diversity in the neural basis for cold, it is remarkable majority vivo dependent on menthol receptor transient potential melastatin 8 (TRPM8). TRPM8-null mice deficient temperature discrimination, detection noxious temperatures, injury-evoked hypersensitivity nocifensive cooling compounds. To determine how TRPM8 plays such critical yet diverse role signaling, we generated expressing genetically encoded axonal tracer neurons. Based expression, neurons bear neurochemical hallmarks Aδ-fibers, presumptive nociceptors non-nociceptors. More strikingly, axons diffusely innervate skin oral cavity, terminating zones contain nerve endings mediating perceptions innocuous cool, first- second-cold pain. These results further demonstrate circuitry sensing cellularly anatomically complex, suggests fibers, caused neuronal context use single molecular sensor convey wide