It is rare for researchers to be able to say their discovery has rewritten textbooks, but a group of scientists who have found how brain cells react to warm temperatures may get that opportunity. This long-sought find overturns the textbook explanation for how warmth is detected and offers a more elaborate understanding of thermoregulation, the essential process of regulating body temperature.
How Body Temperature is Regulated
For around 80 years, a small region of the brain known as the preoptic hypothalamus (POA) has been recognized as the site used for detecting warmth. How this happens has been a much more difficult thing to understand. The POA is also responsible for a number of different and complex behaviors, such as eating or sleep, which has made pinpoint identification of the cells and brain circuits behind warmth detection tricky to find. The current model, and the one described in most influential textbooks, is that the POA is able to detect and respond to subtle changes in the body’s core temperature.
What the Researchers Found
The UC San Francisco-based research went on in a few different stages, each one building on the previous to create the final findings. It all began when the researchers, using a tool called “phosphoTRAP”, looked for the genes that were the most active within the POA cells of mice when placed in a warm environment. This produced two genes, called PACAP and BDNF. Some fluorescent marking ensued, which found that there was a significant overlap between the cells expressing PACAP or BDNF and suggested a distinct neuron population.
Operating under the suspicion that these could be warmth-sensing cells, the researchers engineered a way to monitor cell activity with fiber optics. The mice were then placed in a chamber that could have its temperature quickly changed. The fiber optic recordings showed the PACAP/BDNF cells becoming active in response to temperature increases.
Now, the part that prompted all of the “rewriting textbooks” talk is that these cellular activity changes occurred within seconds. This type of speed wouldn’t be possible if the POA cells were responding to the body’s core temperature. Instead, it suggested to the researchers that the thermal sensory receptors in the skin were sending signals to the POA directly. To confirm this, the researchers applied capsaicin (the thing that makes chili peppers “hot”) to the skin. One of the proteins in capsaicin is known to trigger sensors in the skin in a similar manner to real heat, and a connection between this trigger and the PACAP/BDNF cells was found.
When the researchers began using light to stimulate the PACAP/BDNF cells directly, they noticed that the body temperature of the mice started declining rapidly regardless of how warm their environment was. This was because the cell stimulation was triggering a series of cooling behaviors such as sweating and panting or seeking a cooler spot to rest in.
What This Means
Together, this collection of findings suggests that the brain cells of the POA region, which contain both PACAP and BDNF genes, are involved in responding to warm temperatures. They do this thanks to sensory information received directly from the skin, rather than in response to shifts in the body’s core temperature. This is an intriguing and important set of findings, and the researchers should be congratulated on their achievement.
Tan, C., et. al., “Warm-Sensitive Neurons that Control Body Temperature,” Cell, 2016; http://dx.doi.org/10.1016/j.cell.2016.08.028.
Farley, P., “Long-Sought ‘Warm-Sensitive’ Brain Cells Identified in New Study,” UCSF web site, September 8, 2016; https://www.ucsf.edu/news/2016/09/404046/long-sought-warm-sensitive-brain-cells-identified-new-study, last accessed September 12, 2016.