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Introduction to Behavioral Neuroscience

16.3 Neural Control of Core Body Temperature

Introduction to Behavioral Neuroscience16.3 Neural Control of Core Body Temperature

Learning Objectives

By the end of this section, you should be able to

  • 16.3.1 Describe the reasons why animals need to maintain homeostasis for core body temperature.
  • 16.3.2 Describe the neural components of homeostatic systems that regulate core body temperature.

Although we don’t often think about it, modern day humans routinely make behavioral choices to regulate their body temperatures. Our homes and other buildings have thermostats to ensure that our living environments are not too hot or cold. We wear warm jackets in the winter and dress light in the summer—especially in warm places like the beach. We almost always prefer to take warm showers instead of cold showers and enjoy warm visits to the sauna or hot tub. It feels great to warm up with a cup of hot chocolate on a chilly afternoon or to drink a cool glass of lemonade on an especially hot day.

Other animals aren’t so lucky—they must generate warmth from their own metabolism and/or find appropriate shelters and life-sustaining environments to meet their thermoregulatory needs. Mammals (including humans), birds, and some species of fish are endotherms, deriving heat primarily from metabolism (Figure 16.10). Producing heat from within the body is energetically “expensive,” and therefore endothermic animals need to consume a sufficient amount of calories just to maintain their core body temperatures. Other animals, including lizards, amphibians, and other species of fish, are ectotherms, deriving heat primarily from their environment. They do not need to consume as many calories as endothermic animals with similar body weights, but they tend to stay in places that allow a constant source of heat, such as near a body of water or on structures that face the sun.

Photos of endotherms (bird, cat, dog) and ectotherms (frog, axolotl, chameleon). Endotherms, like mammals and birds, create heat via metabolism. Ectotherms, like lizards and amphibians, must get heat primarily from their environment.
Figure 16.10 Endotherms vs ectotherms Cardinal By Jocelyn Anderson - Imported from 500px (archived version) by the Archive Team. (detail page), CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=71588300, Frog By Jacob W. Frank - NPGallery, Public Domain, https://commons.wikimedia.org/w/index.php?curid=105409865, Axolotl By Tinwe from Pixabay - https://pixabay.com/photos/axolotl-leucistique-male-ambystoma-2193331/, CC0, https://commons.wikimedia.org/w/index.php?curid=93523985, Chameleon reproduced with permission from Dr. Tyler Dause and Dr. Emma Thompson. Cat reproduced with permission from Elizabeth Kirby. Dog reproduced with permission from Bryon Smith.

Body temperatures also increase in response to increases in physical activity, such as going for a run or lifting weights. During strenuous physical activity, the body must respond to increases in core body temperatures via changes in physiology and behavior to release excess heat and cool down.

Regulation of core body temperature is highly important for survival. Maintaining core body temperatures within a narrow range is necessary for the structural integrity of cells and optimal biochemical dynamics throughout the body. All animals employ homeostatic mechanisms to ensure that their core body temperatures do not rise or fall outside an optimal range. Mammals have evolved the ability to sense temperature both throughout their outer body surfaces and within their inner core and, when necessary, engage in a variety of physiological and behavioral mechanisms to restore homeostasis.

Neural sensation of body temperature

The feeling of warmth from sitting by a fire or the feeling of cold from stepping outside on a windy, winter day seems so natural and instinctive… it can be easy to forget that the nervous system must measure these temperatures and cause the sensations of “hot” and “cold.” How does the nervous system measure external temperatures?

Specific neurons measure body temperature by expressing specialized ion channels that only open and allow ion flow in response to narrow temperature ranges. These temperature-gated ion channels are a subset of a family of ion channels called “Transient Receptor Potential (TRP)” channels, commonly referred to as thermoTRPs (Figure 16.11) (see Chapter 9 Touch and Pain).

TRP ion channels open in response to different ranges of temperature (and some chemicals from plants). Display showing the temperature ranges that activate temperature-sensitive channels (TRPs). Channels in order of lowest temperature of activation: Cold range: TRP1A, TRMP8, TRPM3. Hot range: TRPV4, TRPV3, TRPV1, TRPV2. Photo of mint plant and chili peppers also shown on cold and hot sides, respectively.
Figure 16.11 TRP ion channels that regulate body temperature TRP ion channels open in response to different ranges of temperature (and some chemicals from plants). Image credit: Mint: By Arjot, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=92119526. Chili: By Kmtextor, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=83424742

Once open, these ion channels allow positively charged cations to pass through the membrane and cause depolarization within neurons. For example, the TRPV1 ion channel opens at temperatures around 42 °C. Therefore, neurons that express TRPV1 alert the nervous system that a nearby stimulus is above a core body temperature of 37 °C. In contrast, the TRPM8 ion channel opens in response to temperatures at and below 22 °C, indicating the presence of a stimulus much cooler than core body temperature. Multiple TRP channels have been discovered that exhibit their own temperature ranges for activation, and the combination of these thermoTRPs allow the nervous system to determine environmental and internal temperatures.

Amazingly, many of these TRP channels can also open upon exposure to certain chemical compounds that are naturally produced by plants (see Chapter 8 The Chemical Senses). For example, TRPV1 channels open in response to capsaicin, a chemical naturally produced by chili peppers. Because neurons that express TRPV1 cannot distinguish between a naturally warm stimulus and capsaicin, foods with chili peppers cause the sensation of heat whether they are actually warm or not. Likewise, TRPM8 channels open in response to menthol, a chemical produced naturally in mint leaves. Therefore, foods and products (such as mouthwashes) containing menthol feel cold even if they are at room temperature.

Neural systems that sense and control thermoregulation

Temperature in mammals seems to be sensed via two independent systems. One system senses changes in temperature along the external surface of the body (such as the skin and mouth) and functions primarily in the conscious detection of hot or cold stimuli from the environment. The other system senses changes in core body temperature and functions primarily in regulating the temperature of the internal environment.

Temperature at the body surface is measured by specialized neurons in the dorsal root ganglia (for the lower body) or trigeminal ganglia (for the head). These neurons send sensory projections to the body surface that express thermoTRP ion channels in the skin (Figure 16.12). When specific thermoTRP ion channels open in response to environmental temperatures, the neurons that express them increase action potential firing frequency, ultimately releasing excitatory neurotransmitter onto neurons in the spinal cord. This information is relayed to the somatosensory cortex for the conscious perception of temperature. Using these neural circuits, animals can detect changes in temperature at specific body locations. For example, picking up a hot mug of coffee or a cold glass of water causes the perception of temperature change specifically on the hand. If you step into a warm shower or jump into a cold lake, peripheral sensors will indicate a change in environmental temperature from all over the body surface.

Peripheral nerve endings with thermosensitive channels send information to the spinal cord and then to the brain. Diagram of a sensory neuron with thermosensitive nerve ending in a block of skin sending input to a spinal cord neuron, which in turn connects to a neuron in the middle of the brain, which then sends a connection out to the lateral surface of the brain.
Figure 16.12 Sensation of body temperature in the skin Peripheral nerve endings with thermosensitive channels send information to the spinal cord and then to the brain.

Core body temperature, the temperature of the internal environment of an animal, is measured directly in the brain by neurons in a region of the hypothalamus called the pre-optic area (POA) (Figure 16.13). The POA is sensitive to the temperature of the blood that flows within the blood vessels surrounding these neurons. Because blood travels throughout the internal organs before reaching the POA, the blood temperature within the POA is likely to be indicative of the overall body temperature. Some POA neurons increase action potential frequency in response to relatively warm core body temperatures—the warmer the blood, the greater the action potential frequency. A separate group of POA neurons increase activation in response to colder core body temperatures.

Left shows flowchart of feedback when body temperature is too cold. Right shows flowchart of feedback when body temperature is too hot. Feedback is described in detail in the main text. Photo of penguins huddling shown with behavioral changes to cold temperatures. Photo of dog panting shown with behavioral changes to hot temperatures. Diagrams of POA, adipose tissue and a blood vessel also shown to emphasize the roles of these structures.
Figure 16.13 Neural regulation of body temperature Penguins image: Image by Struthious Bandersnatch, 1988. Emperor penguin chicks at Sea World, by Jose Lopez Jr. U.S. Air Force, Public Domain; Dog reproduced with permission from Bryon Smith.

Neurons that measure body temperature from specific parts of the periphery also send information to the POA. Therefore, the POA senses information about core body temperature and peripheral body temperatures to ultimately function as a control center that maintains temperature homeostasis. Interestingly, some POA neurons also function in the allostatic increase of body temperature experienced during a fever to overcome a virus or bacterial infection (see the feature box on Investigating allostasis of body temperature during illness).

Effector systems that regulate thermoregulation

If core body temperature deviates from a set point, how does the nervous system cause a change that restores a healthy value? Mammals employ numerous physiological and behavioral mechanisms to regulate body temperature. Both the warm-sensitive and cold-sensitive neurons within the POA project axons throughout the brain that, in response to an increase in action potential frequency, engage different effector systems (Figure 16.13).

One way in which the POA regulates temperature is to cause changes in physiological effector systems. These changes are often unconscious and regulated by the autonomic nervous system. For example, in response to cold internal body temperatures, cold-sensitive POA neurons in mammals activate effector neurons in the sympathetic nervous system that increase body heat. The sympathetic nervous system increases heat primarily by stimulating brown adipose tissue (BAT), fat cells that increase metabolic activity to release heat. Increasing sympathetic tone also constricts blood vessels so that warm blood does not lose heat to the external environment. In contrast, when body temperature becomes too high, warm-sensitive POA neurons decrease sympathetic tone, decreasing BAT thermogenesis and causing vasodilation of blood vessels to release excessive heat.

The POA also regulates temperature by causing changes in animal behavior. In response to cold internal body temperatures, cold-sensitive POA neurons cause an unpleasant cold sensation that motivates an animal to seek and conserve heat. Think about how uncomfortable it can be to feel cold—this aversive behavioral drive causes animals to relocate to warmer locations, such as places exposed to sunlight or other sources of heat. Animals can also change posture to decrease the exposed surface area of their bodies, thereby minimizing heat loss to the environment. Finally, animals engage in species-specific behaviors such as shivering, huddling with other individuals, or nest building to increase heat. In response to warmer temperatures, warm-sensitive POA neurons similarly cause an unpleasant warm sensation that motivates animals to cool down by seeking cooler, shady environments. Many animals change their postures to expose their skin to the outside air and release heat to the environment. Some species also engage in licking their bodies, panting, or sweating.

Investigating allostasis of body temperature during illness

During viral or bacterial infection, mammals exhibit a temporary increase in core body temperature (a fever) to try to destroy the foreign pathogens. This period of allostasis can last hours or days depending on the severity of the infection. Do the same neurons that play a role in temperature homeostasis also increase body temperature during illness?

A recent study (Osterhout et al., 2022) identified neurons active during infection. To cause an infection, mice were injected with a compound called lipopolysaccharide (LPS) that mimics a bacterial infection (Figure 16.14) (see Chapter 17 Neuroimmunology) caused an increase in body temperature, while ablating these neurons greatly reduced body temperature during infection. Therefore, these VMPO neurons are thought to be specialized to detect infection and are sufficient and necessary to generate fever by projecting to the POA neurons that normally increase body temperature.

Three-part diagram. 1) Left shows diagram showing mice were injected with LPS to mimic a bacterial infection and cause fever. Right shows coronal brain slice of mouse, with VMPO highlighted in the ventral area near the 3rd ventricle. Mice injected with LPS showed greater activation of VMPO neurons than vehicle-injected mice. 2) Left shows diagram showing mice expressing excitatory chemogenetic DREADD receptors in VMPO neurons were injected with CNO to induce VMPO neuron firing. Brain slice with VMPO highlighted is shown, similar to part 1. Right shows bar graph revealing that VMPO activation with CNO led to an increase in body temperature. 3) Left shows diagram showing mice with VMPO lesions were injected with LPS. Right shows bar graph revealing LPS causes increased body temperature in sham mice. Mice with VMPO lesions do not show LPS-induced body temperature increases.
Figure 16.14 VMPO activity regulates body temperature

Interestingly, other areas of the brain have been discovered that also become activated during infection, such as a population of neurons in the brainstem (Ilanges et al., 2022). How different populations of neurons throughout the brain coordinate allostasis in response to illness is an active area of investigation and may lead to insights to help patients with a severe response to infection.

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