Mice with a cool touch

Chill out; you can use the same brain region to sense temperature and touch.

The feel of an object and its temperature are interpreted by the same region of the brain, a new study by researchers at the MDC and Charité – Universitätsmedizin Berlin has shown. The research, published in Nature Neuroscience, reveals details of how we detect small changes in temperature and provides a mechanism to explain the illusion known as Weber's effect.

A mouse paw seen from very close. Picture: Poulet lab

We sense temperature through nerve endings in our skin, which send information to the brain allowing us to respond to our environment. Neuroscientists have found that we perceive mild warming or cooling differently from the painful sensations felt when we touch something very hot or very cold. What isn't so well understood is exactly how we detect temperature in the skin, which nerve fibres send this information to the brain, and which parts of the brain are responsible for interpreting the information. Dr James Poulet and his team set out to clarify the circuits for cooling perception in mice.

Poulet's research focuses on the cortex of the brain and its role in sensory perception. “Mice are an ideal subject for these studies,” Poulet explains, “because their genetics are well understood, and we can study their behaviour.” But unlike human subjects, mice can't tell us when they notice a change in temperature, and to study perception in mice scientists need to measure a fast behavioural report of a stimulus. Previously researchers have used indirect evidence that mice perceive temperature with their skin, for example preferring to spend time on a warmer part of a floor. Poulet and his team refined this by training mice to respond immediately to temperature changes by licking when they felt a cool sensation on their forepaw. The mice could perceive cooling of just two degrees below skin temperature, which is very similar to what we humans can detect.


To find out which region of the brain the mice were using to perceive cooling, the researchers used intrinsic optical imaging. They found cooling activated the primary sensory cortex. Interestingly, the same region was also activated by tactile stimulation – touch and temperature were activating the same part of the brain. The researchers confirmed this with measurements of individual neurons, which also responded to both touch and temperature. “This is significant,” says Poulet. “It demonstrates that it's not just the same brain region responding to temperature and touch, but that individual neurons can detect both signals.”

The overlap between the sensations of touch and temperature doesn't entirely come as a surprise – you can demonstrate the link with the Weber's effect illusion. To try this at home, take two coins and put one in your pocket and the other in the freezer for a minute or two. Now ask a friend to judge, with closed eyes and outstretched hands, which coin feels heavier. Weber's effect says that the cold coin will feel heavier than the warm one, even though they have the same weight.

Our perception of the feel of an object and its temperature are inseparable, which suggests our brain is able to put together tactile and thermal senses. So it makes intuitive sense that the same nerves in the sensory cortex detect both sensations.

Before the sensory cortex perceives temperature, it must be detected by proteins in nerve endings in the skin, starting with a signal that travels to the brain via the spinal cord. Poulet and his team collaborated with other neuroscientists at the MDC to investigate these mechanisms.

The key temperature-sensing protein for cooling is TRPM8. It's the sensor that's fooled by menthol into sending cool signals when you chew peppermint-flavoured gum or use Vicks VapoRub. Menthol doesn't actually cool your skin, it just activates TRPM8 which you perceive as a cool temperature.

Working with Trpm8 knockout mice, which lack the gene for this cold-responsive protein, the researchers found the knockout mice could not learn to lick in response to a cool forepaw stimulus . “This demonstrates directly that this protein is required to perceive cooling,” says Poulet.

To measure which nerve fibres carry the signal from the skin towards the brain, Gary Lewin's lab, also at the MDC, compared wild type and Trpm8 knockout mice. The researchers found that C fibres, traditionally known for signalling pain, responded to cooling in wild-type mice. The knockout mice lacked cooling responses in these fibres.

Putting the results of these different experiments together gives us insight into how we perceive temperature. It demonstrates that TRPM8 is required to sense cooling and that cooling signals travel via C fibres, which are traditionally known for their role in pain. In the brain, the cool stimulus is perceived by the sensory cortex which also responds to touch.

“Combining sensory information to create a coherent perception of the world is one of the fundamental roles of the cortex,” says Poulet. The discovery that single neurons within the sensory cortex can detect stimuli from multiple senses begins to reveal how our brain integrates sensory information.

- Arwen Cross

Highlight Reference:

Milenkovic N, Zhao WJ, Walcher J, Albert T, Siemens J, Lewin GR, Poulet JFA. A somatosensory circuit for cooling perception in mice. Nature Neuroscience 17(11): 1560-6 (November 2014). doi:10.1038/nn.3828

Featured Image: A close-up picture of a mouse paw. Photo: J. Poulet, MDC