Animals continuously sense the temperature in their environment, which is crucial for survival and for maintaining an optimal energy expenditure. Thermal perception is enabled by sensory afferent neurons that innervate the skin and express molecules that transduce thermal stimuli into electrical signals, which are later processed by the nervous system. In the recent years, studies in genetically modified mice have found sensory afferents and ion channels that transduce cooling in mammals, but the perceptual ability of mice to sense warmth and the underlying encoding mechanisms remain unknown.
In this work, I have investigated the neurobiological mechanisms that underlie the perception of warmth. To do so, I have employed the mouse (Mus musculus) as a model system due to both the phylogenetic proximity to humans and the availability of genetic tools for mechanistic studies.
Using a sensory detection behavior, I first show that mice perceive tiny (0.5oC) changes in temperature of the forepaw. Like humans, mice are able to discriminate warming from cooling, they are less sensitive to warmth and the baseline temperature strongly impacts the perceptual saliency. Together, these data indicate that mice and humans share many features of thermal perception, suggesting common sensory coding mechanisms.
Cooling perception in mice is known to require cool-activated sensory afferents that express the channel TRPM8, but the neurons encoding warmth are unknown. Here, warming recruited two polymodal afferent populations: one fired upon warming (warm-activated) and the other was both warm-silenced and cool-activated. To investigate their role in perception, I used gene knockouts and optogenetic afferent stimulation and found that mice sense and encode warming without the warm-activated ion channels TRPV1, TRPM3, TRPA1 and TRPM2. However, surprisingly, despite TRPM8+ afferent stimulation evoked a cooling percept, TRPM8-null mice cannot detect warming. Trpm8-/- mice possess warm-activated afferents but lack warm-silenced neurons, suggesting that cooling input from warm-inhibited fibers is required for warmth perception.
In preliminary work I have also investigated the role of primary somatosensory cortex in warm perception. Using intrinsic optical imaging I observed that cooling and touch, but not warming, elicits robust responses; but silencing of this brain region impaired the perception of warming stimuli.
Altogether, the data from my thesis suggest that warming perception is an integrative process and requires input from both warm- and cool-activated sensory pathways.
