July 24, 2018
Written by: Sarah Reitz
No matter where you live, chances are you’ve experienced more than a few days of extreme heat this summer already. When temperatures rise, it’s critically important that all animals, including humans, are able to regulate their body temperatures. This is because so many of the crucial biological processes that occur throughout our bodies are optimized to take place within a narrow range of temperatures (usually 97- 99° F). Outside of this range these processes come to a halt, ultimately leading to extreme damage or even death. While cold-blooded animals like reptiles must regulate their body temperature using external sources of heat or cold, birds and mammals have the ability to regulate their internal temperature independent of their surroundings. So when our body temperature starts to climb — whether it’s from being outside on a hot day or sweating it out at the gym — how does our body know to cool itself off?
Warm-sensing neurons are found throughout the body
It may not surprise you to learn that there are temperature-sensing neurons in our body that are able to sense and respond to high temperatures (known as “warm-sensing neurons”). Anyone who has sat on a leather car seat on a hot day could tell you that we most definitely can sense heat through our skin! These warm-sensing neurons in our skin are part of a larger set of warm-sensing neurons, scattered throughout our peripheral nervous system, outside of the brain and spinal cord. These neurons measure the temperature of various tissues throughout the body, with the skin and internal organs in the abdominal cavity being the most important peripheral sources.
These peripheral warm-sensing neurons are not alone, however. There is actually a second set located inside the central nervous system (CNS), constantly detecting our internal temperature even though we are not consciously aware of it1. This set is found in both the spinal cord and in a region of the brain called the hypothalamus (Figure 1), and is continually monitoring the temperature of our central nervous system. In fact, between 20%-40% of neurons in the preoptic area — a region in the hypothalamus — are thought to be warm-sensitive2,3! We know that both the central and peripheral warm-sensing neurons play a role in controlling our body temperature because heating either set by only a few degrees causes temperature regulation processes to begin (such as sweating and widening of the blood vessels, called vasodilation). Like any good teammates, these two sets of neurons are constantly communicating with each other, with the CNS warm-sensing neurons also receiving information about our body temperature from the peripheral set of sensors. When both peripheral and central warm-sensing neurons are heated simultaneously, this communication between the groups results in an even stronger thermoregulatory effect than just heating one set alone1. This is extremely advantageous because elevated temperatures in both your periphery and in your central nervous system signal a much larger heat threat, greatly endangering crucial proteins and cellular processes across the brain and body, that must be dealt with more rapidly compared to an elevated temperature in only one location.
The hypothalamus acts as a “central thermostat”
The communication between both sets of warm-sensing neurons means that not only does the hypothalamus sense our brain’s temperature, but it also gets information about the temperature in the rest of our body. In this way, the hypothalamus acts as a sort of central thermostat, gathering information about the temperature throughout our body and then responding appropriately to cool it down. While at first it may seem a little odd to have temperature-sensing neurons deep in the brain, when we look at the location of the hypothalamus it actually reveals a near ideal location for a thermostat in the body. It is located directly above the major blood supply to the brain, and directly next to ventricles carrying cerebrospinal fluid (CSF) throughout the brain. Together, this means that the hypothalamus receives temperature information from peripheral warm-sensing neurons and integrates that with its own temperature information not only of its own tissue, but also of its blood supply and CSF!
So how does this hypothalamic thermostat operate? As mentioned earlier, our body has a natural “setpoint”, or temperature at which is functions at the highest level. Similar to the thermostats found in home across the world, when our body’s temperature rises above this setpoint, the warm-sensing neurons are activated and begin to fire more action potentials, signaling to the hypothalamus that the body is getting too warm4. While it is still unknown exactly what allows these neurons to respond to warmth, some recent research suggests it may be due to the presence of specific ion channels that are activated by heat (among other things), called TRP channels2. Ion channels are a type of protein that when open, allow charged particles (called ions) to flow through them. When enough positive ions enter a neuron, it fires an action potential, or electrical signal used to communicate with other neurons. Heat causes specific types of TRP channels to be open more often, so a neuron that expresses these TRP channels will have more positive ions entering when it is exposed to heat compared to when it is cooler, causing the neuron to fire more when it is warm..
When the hypothalamus receives this message from the warm-sensing neurons, it initiates a series of thermoregulatory responses, which can be divided into two broad categories. The first category is physiologic responses, which are involuntary. These include processes such as sweating and vasodilation (dilation of the blood vessels to disperse heat away from the body). Animals who don’t sweat, like dogs, will cool themselves by panting, while rodents spread saliva on their fur so that it can evaporate and cool them off1,5. Interestingly, you will always vasodilate before you begin to sweat, most likely because vasodilation is less “costly” to the body. When the weather gets hot, you want to conserve as much water as you can, so sweating will only happen if absolutely necessary! The second category of thermoregulatory responses is behavioral responses, which are motivated behaviors. These include actions such as finding a shady place to sit when it’s hot out, or — if you’re like my cat — sitting in front of the AC unit.
Exactly how the hypothalamus signals for these thermoregulatory processes to begin remains unknown. However, given how crucial temperature maintenance is for our body it seems likely that there are multiple pathways involved in order to not only produce but also coordinate the many thermoregulatory processes that occur when we get hot. For instance, signaling pathways to produce vasodilation of our blood vessels must occur alongside with signals to sweat glands telling them to produce sweat, to name a few. Making this question even more complicated is the fact that our body’s temperature setpoint changes in response to many factors6. For example, when our body is sick it will mount a fever response to attempt to fight off the infection. How does our hypothalamus know to increase our setpoint past its normal limits, and that this temperature increase is different from a temperature increase caused by exercise? As researchers develop new tools to explore and trace neural circuits, hopefully we will further understand how our small hypothalamus can integrate information from so many different places. After all, ever-changing temperatures (in our environment and in our body!) are something that is impossible to escape!
Cover Image: from digitalphotolinds via Pixabay, Creative Commons CC0. https://pixabay.com/en/weather-temperature-hot-summer-120-1216041/
Figure 1: from Anatomography by Life Science Databases via Wikimedia Commons, Creative Commons Attribution-Share Alike 2.1 Japan. https://commons.wikimedia.org/wiki/File:Hypothalamus.gif
1. Tan C & Knight Z. (2018) Regulation of body temperature by the nervous system. Neuron 98(1):31-48.
2. Song K, Wang H, Kamm G, et al. (2016) The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia. Science 353(6306)1393-1398
3. Griffin JD, Boulant JA (1995) Temperature effects on membrane potential and input resistance in rat hypothalamic neurones. J Physiol 488(Pt 2):407–418.
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5. Magoun HW, Harrison F, Brobeck JR, Ranson SW (1938) Activation of heat loss mechanisms by local heating of the brain. J Neurophysiol 1:101
6. Morrison S (2016) Central control of body temperature. F1000 Research Faculty Review 800 doi: 10.12688/f1000research.7958.1