The Sensory Coding of Warm Perception.

Area of Science:

• Neuroscience
• Sensory Biology
• Mammalian Physiology

Background:

• Humans and mice can detect minute changes in skin temperature, distinguishing between warm and cool sensations.
• The neural mechanisms underlying warm perception, particularly the role of specific ion channels and nerve fibers, remain incompletely understood.

Purpose of the Study:

• To investigate the neural pathways and molecular mechanisms responsible for detecting skin warming in mice.
• To determine if established thermosensitive ion channels contribute to warm perception.

Main Methods:

• Electrophysiological recordings from polymodal C-fibers in mice.
• Behavioral studies using genetically modified mice lacking specific thermosensitive ion channels (TRPM2, TRPV1, TRPM8).
• Pharmacological silencing of TRPM8 channels in vivo.

Main Results:

• Two distinct populations of polymodal C-fibers were identified that signal warm stimuli.
• Warm excitation of one C-fiber population and suppression of a cool-driven population contribute to warm detection.
• While TRPM2 and TRPV1 channels partially influence warm perception, TRPM8 channel absence or silencing completely abolished warm detection.
• Triple mutant mice lacking noxious heat sensation could still detect skin warming, though with reduced sensitivity.

Conclusions:

• Warm perception in mice is not explained by a simple labeled-line model.
• A conserved dual sensory model, involving both warm-excitable and cool-suppressible C-fibers, is proposed for unambiguous skin warming detection.
• The cool-sensing TRPM8 channel plays a critical, non-intuitive role in detecting warm stimuli.