Keeping cool on a warm day is not difficult for modern humans, but over the course of evolution many organisms have struggled to survive in frequently-changing temperatures. They've developed thermoregulation, a biological process allowing for regulation of body temperature towards homeostasis. A small region of the brain's hypothalamus begins this vital regulation by detecting environmental temperature, then induces physiological changes that adjust the animal's core temperature. Unfortunately, the specific neurons that initially detect environmental temperature and kick-start this thermoregulation process have eluded researchers. However, a recent report by Zachary Knight's lab at UCSF (Cell 167, 47–59; 2016) describes novel findings of molecularly-defined warm-sensitive neurons (WSNs) in the hypothalamus of mice, presenting new methods to help understand the process of thermoregulation.

The UCSF team began their study by searching for molecular markers of WSNs. After placing mice in a warm environment (36° C), the researchers took advantage of ribosomal changes in neurons after activation to specifically examine the mRNA sequence of these cells. They observed two genes that were highly co-expressed in cells activated by warmth, providing the first genetic access to WSNs of the hypothalamus.

Next, the team sought to understand the function of these cells in vivo. They injected a virus containing a calcium reporter into the hypothalamus of mice and used fiber photometry to observe the activity of WSNs. When the mice were placed in a temperature-changing chamber the fiber photometry showed that temperature increases were tightly coupled with WSN activity. The authors also used their genetic access to express a specialized channel opsin in WSNs for direct control over the neuron's activity. The researchers observed that direct activation of the WSNs caused a quick decline in core body temperature of the mice, simultaneous changes in thermoregulation behavior like tail vasodilation, and even affected the animal's nest building behaviors. These are all actions associated with a bodily desire to cool down. Thus, the animals were apparently perceiving the heat associated with WSN activation, even when the environmental temperature was held at normal levels.

This finding provides a novel method of controlling the core body temperature and behaviors of animals, along with a new path of research into thermoregulation. But the methods could also be translated into clinical applications, eventually providing doctors and veterinarians new and valuable techniques for controlling a patient's body temperature.