Learning Objectives
By the end of this section, you should be able to
- 16.5.1 Describe the reasons why animals need to maintain homeostasis for water.
- 16.5.2 Describe the neural components of homeostatic systems that regulate water balance and drinking behavior.
Consider how interesting (or uninteresting) water is as a stimulus. Colorless, odorless, tasteless… By definition, water is about as neutral a stimulus as one can imagine. Most of the time, we don’t think of water as rewarding. We often walk past drinking fountains and water coolers without feeling like we are missing a valuable opportunity. However, when we don’t have enough water in our bodies, drinking water becomes highly rewarding. The feeling of being thirsty is very unpleasant and the longer we go without water, the more extraordinary lengths we will go to take a drink.
Mammals are composed mostly of water. Over half of a human’s body weight is water, with approximately 65% located within the body cells, 28% in the extracellular fluid, and 7% in the blood. Maintaining an appropriate amount of water in our cells and surrounding fluids is critical for maintaining the structural integrity of cells and for providing an aqueous environment for the solutes (nutrients, ions, and biomolecules) that make life possible.
Water enters and leaves cells by the process of osmosis—the diffusion of water across a membrane from regions of low solute concentration to regions of high solute concentration (Figure 16.25). The unit of measurement of solute concentration within a solution is osmolarity, the number of moles of solute per liter of solution. Mammalian cells have an osmolarity of approximately 300 mOsm/L. If cells are surrounded by a solution of equal osmolarity, the environment is said to be isotonic, and there is no net water flow in or out of the cell. However, if the cell is surrounded by a solution that has a higher solute concentration, the environment is hypertonic. In these conditions, water will flow from inside the cell to the extracellular fluid, causing the cell to shrink. In contrast, if the cell is surrounded by a solution that has a lower solute concentration, the environment is hypotonic, and there is net movement of water from outside the cell to the cytoplasm. This state can cause the cell to swell up and even burst. Therefore, osmotic homeostasis systems must ensure that the blood and extracellular solutions are stably maintained at 300 mOsm/L.
To maintain osmotic homeostasis, animals must measure the osmolarity of the blood and ensure that the amount of water lost over time is equal to the amount of water gained over time. Our bodies constantly lose water over time due to evaporation and the need to urinate metabolic waste products. Although animals can generate some water molecules on their own via the process of cellular respiration, most mammals obtain water primarily by ingesting liquids. When the osmolarity of the blood becomes too low, homeostatic systems motivate us to excrete more water in the urine (having to pee!). When the osmolarity of the blood becomes too high, homeostatic systems motivate us to consume water—a process we describe as being thirsty.
Osmotic homeostasis systems
Mammals sense blood osmolarity within a brain structure called the subfornical organ (SFO) (Figure 16.26). Some SFO neurons increase action potential frequency when the blood becomes hypertonic, while others increase neural activity when the blood becomes hypotonic. These two populations of neurons within the SFO project to other hypothalamic populations including the organ vasculosum of the lateral terminalis (OVLT). Together, the SFO and OVLT control the neural response to osmotic change.
For example, if you ingest food that is high in solutes (such as a handful of salty crackers), the solutes become absorbed by the bloodstream and can increase the hypertonicity of blood. Likewise, if you have not consumed water in a relatively long time (multiple hours), the blood also risks becoming hypertonic. In response to hypertonic conditions, the SFO and OVLT activate effector systems to increase the amount of water within the blood (Figure 16.26). One method of increasing water is to motivate an animal to drink by creating the sensation of thirst—an unpleasant condition in which the tongue dries and the act of swallowing liquids becomes highly rewarding. Thirst is a complex motivational state mediated by multiple downstream areas, including regions of the cerebral cortex and limbic areas. How neurons in these structures collectively coordinate the aversive feeling of being thirsty is an active area of investigation.
In addition to causing changes in behavior, the SFO and OVLT can cause a physiological response that results in less water loss in the urine (Figure 16.26). In response to hypertonic states, the SFO and OVLT cause an increase in the release of antidiuretic hormone (ADH) from the pituitary gland. This hormone primarily acts on cells within the kidney to release less water into the urine. This regulation of urine water content is why the color of urine can change depending on hydration state—the more water you drink, the less ADH is released from the pituitary, and the clearer your urine will become! Dysregulation of the ADH system (for example, mutations in the gene that encodes ADH or the ADH receptors in the kidney) disrupt osmotic homeostasis by causing abnormal water loss and urine formation by the kidneys. This disorder, called diabetes insipidus, can cause severe dehydration and constant thirst if untreated.
Interestingly, regulation of osmotic balance has a feed-forward mechanism, in which a homeostatic response occurs before there is actually a change in the system (see feature box on Studying feed-forward mechanisms in thirst). For example, if you feel thirsty and drink a large glass of water, sensors on the tongue detect the ingestion of water and cause a change in SFO neural activity before the water is actually absorbed into the bloodstream from the digestive tract. This mechanism allows you to feel satiated immediately when taking a large drink of water—otherwise, you would have to wait several minutes to feel the effect. In this way, homeostasis can be maintained faster than normal digestive processes would otherwise allow.
Neuroscience in the Lab
Studying feed-forward mechanisms in thirst
Neuroscientists have studied the effect of environmental stimuli on activity in SFO neurons using fiber photometry, a form of calcium imaging. SFO neurons can be made to express a transgene, GCaMP, that fluoresces proportionally to Ca2+ release inside the cell. This Ca2+ signal is a reflection of neural activity (see Methods: In Vivo Calcium Imaging). An optical fiber is placed directly above SFO neurons to measure changes in SFO activity in freely moving, behaving mice (Figure 16.27).
A recent study (Zimmerman et al., 2016) showed that SFO neurons increase or decrease activity immediately when mice are allowed to ingest certain substances, much faster than digestive processes. For example, in thirsty mice, when SFO activity is already relatively high, SFO activity decreases immediately when mice are allowed to drink water. In fact, SFO activity decreases even more if the water is cold. This result might explain why drinking cold water is so much more satiating when we are thirsty compared with water served at room temperature. In contrast, SFO activity increases immediately when mice consume solid chow, likely a mechanism to anticipate the need for water before the food is actually absorbed by the digestive track into the bloodstream. Taken together, these feed-forward mechanisms allow an animal to minimize changes to homeostasis and avoid large deviations from a set point during ingestion of food and liquids during a meal.