How Does Thirst Affect Brain Function and Behavior in Nephrogenic Diabetes Insipidus?

What you need to know

• Thirst is a powerful urge controlled by specific brain regions that affect overall brain activity.
• In nephrogenic diabetes insipidus (NDI), the kidneys can’t respond to a hormone that regulates water balance, leading to excessive thirst and urination.
• New research on how thirst and hunger compete in the brain helps explain symptoms like growth problems and attention difficulties in NDI.

Understanding Nephrogenic Diabetes Insipidus

Nephrogenic Diabetes Insipidus (NDI) is a condition where the kidneys can’t properly conserve water. This leads to the production of large amounts of dilute urine, even when the body is dehydrated. As a result, people with NDI experience intense thirst and need to drink large quantities of water to avoid dehydration.

Children with NDI may show extreme behaviors to satisfy their thirst, such as drinking from unusual sources like flower vases or even toilets if water is not readily available. They also often have problems with attention and growth, though the reasons for these issues have been unclear.

Recent advances in neuroscience have provided new insights into how thirst works in the brain, which helps explain some of the symptoms seen in NDI.

The Brain’s Thirst Centers

Thirst begins in a part of the brain called the lamina terminalis, which is located near the third ventricle, a fluid-filled cavity in the center of the brain. The lamina terminalis contains three important structures:

1. The subfornical organ (SFO)
2. The organum vasculosum lamina terminalis (OVLT)
3. The median preoptic nucleus (MnPO)

The SFO and OVLT are special because they lack the blood-brain barrier, which normally prevents most substances in the blood from entering the brain. This allows these structures to directly sense the concentration of substances in the blood, including how much water is present.

When the body needs water, neurons in the MnPO become excited. These neurons receive input from the SFO and OVLT. Scientists have used a technique called optogenetics, where specific neurons can be controlled with light, to show that activating these MnPO neurons can trigger immediate drinking behavior, even in animals that are fully hydrated.

How Thirst Affects the Whole Brain

Thirst doesn’t just affect a small part of the brain – it has widespread effects on brain activity. Researchers used advanced technology called neuropixels microelectrode arrays to record the activity of thousands of neurons throughout an animal’s brain at once. They found that thirst changed the activity of many neurons in different brain areas.

Importantly, thirst not only affected behavior related to obtaining water but also how the brain responded to other sensory inputs. This helps explain why thirst is such a powerful sensation and why it can affect many aspects of behavior and cognition.

The Competition Between Thirst and Hunger

An age-old question in philosophy is what would happen if a person (or animal) were equally hungry and thirsty. Would they be unable to choose between food and water? Recent research has provided an answer to this question using what’s called “Buridan’s assay,” named after a 14th-century philosopher.

In this experiment, mice were given a choice between food and water after being deprived of both. The results showed that the mice didn’t get stuck – instead, they alternated between eating and drinking in short bursts until both needs were satisfied.

The researchers compared this behavior to a ball rolling in an energy landscape with two wells, one for hunger and one for thirst. If both wells are equally deep (meaning the animal is equally hungry and thirsty), the ball might start in either well by chance. As the animal eats or drinks, the depth of one well decreases, making it more likely for the ball to roll into the other well. This process continues until both needs are met.

Implications for Nephrogenic Diabetes Insipidus

These findings help explain some of the symptoms seen in people with NDI:

1. Attention problems: The constant thirst in NDI means that a large part of brain activity is focused on drinking and maintaining water balance. This can make it difficult to concentrate on other tasks, which may contribute to the higher rates of attention deficit hyperactivity disorder (ADHD) seen in NDI patients.

2. Growth failure: The persistent need for water in NDI may cause the brain to prioritize drinking over eating. In the “energy landscape” model, the thirst well would always be very deep, making it more likely for the person to choose water over food. Over time, this could lead to inadequate nutrition and poor growth.

Conclusions

• New neuroscience research provides insights into how thirst affects brain function and behavior.
• Thirst and hunger compete in the brain, with people alternating between the two needs until both are satisfied.
• In nephrogenic diabetes insipidus, constant thirst may explain symptoms like attention problems and growth failure by affecting overall brain activity and prioritizing water intake over food.

These findings not only advance our understanding of basic brain function but also provide new perspectives on the challenges faced by people with conditions like nephrogenic diabetes insipidus. This knowledge may help in developing better strategies for managing symptoms and improving quality of life for those affected by this condition.