Vasopressin: Predicting changes in osmolality
Two neural circuits control the release of vasopressin in response to eating and drinking before there are any detectable changes in blood water levels.
- Division of Biology and Biological Engineering, California Institute of Technology, United States
The balance between water and solutes in our blood, known as osmolality, must be tightly controlled for our bodies to work properly. Both eating and drinking have profound effects on osmolality in our body. For example, after several bites of food the brain rapidly triggers a feeling of thirst to increase our uptake of water (Leib et al., 2017; Matsuda et al., 2017). In addition, when fluid balance is disturbed, the brain releases a hormone called vasopressin that travels to the kidneys to reduce the excretion of water (Geelen et al., 1984; Thrasher et al., 1981). While much is known about how the brain controls drinking behavior, it is less clear how it regulates the hormonal response.
Vasopressin is primarily secreted by Arginine-vasopressin (AVP) neurons in the supraoptic and paraventricular nucleus of the hypothalamus. These neurons not only respond to actual disturbances in water balance, but also anticipate future osmotic changes that occur after eating and drinking. In 2017, a group of researchers discovered that AVP neurons respond to food and water by rapidly decreasing or increasing their activity, respectively, before there are any detectable changes in osmolality (Mandelblat-Cerf et al., 2017). Now, in eLife, researchers from Harvard Medical School – including Angela Kim as first author and corresponding author Bradford Lowell – report the neural pathways underlying this drinking- and feeding-induced regulation of vasopressin (Kim et al., 2021).
AVP neurons receive signals from the lamina terminalis, a brain structure that detects changes in osmolality and modulates thirst and water retention (McKinley, 2003). Using virus tracing techniques, the team (which includes some of the researchers involved in the 2017 study) mapped neurons in the lamina terminalis that are directly connected to AVP neurons in mice. This revealed that excitatory and inhibitory neurons in two regions of the lamina terminalis (called MnPO and OVLT) send direct inputs to AVP neurons.
Kim et al. then examined whether these neurons in the lamina terminalis responded to drinking and water-predicting cues (such as seeing a bowl of water being placed down; Figure 1). Excitatory neurons that drive thirst and stimulate vasopressin release were rapidly suppressed by both drinking and water-predictive cues before there were any detectable changes in blood osmolality. Conversely, inhibitory neurons showed the opposite response, and were activated following bowl placement and water consumption. This suggests that excitatory and inhibitory neurons in the lamina terminalis help anticipate future osmotic changes by reducing the activity of AVP neurons in response to drinking and water-predictive cues.
Figure 1
How drinking and eating alter the activity of AVP neurons.
AVP neurons (middle) help maintain osmolality by releasing a hormone called vasopressin, which reduces the amount of fluids excreted from the kidneys. Eating and drinking have been shown to alter the activity of AVP neurons before there are any detectable changes in blood osmolality. Water cues (such as the presence of a glass) and drinking suppress the release of vasopressin (red line) by activating inhibitory neurons (blue circle) in the MnPO and OVLT regions of the lamina terminalis. Eating, on the other hand, stimulates AVP neurons to release vasopressin (green line) through an unknown population of neurons (red circle) in the arcuate nucleus, the region of the brain that regulates hunger. These neural circuits allow the body to react quickly to the osmotic changes caused by eating and drinking before the balance of fluids in our blood is disrupted.
Further experiments showed that food intake – but not food-predicting cues – stimulates AVP neurons to release vasopressin prior to an increase in blood osmolality. However, Kim et al. found that neurons in the lamina terminalis are unlikely to be involved in this process, as they did not respond to food consumption as quickly as AVP neurons. Instead, they discovered that these feeding-induced signals came from an undefined neuronal population in the arcuate nucleus, the hunger center in the brain that houses the neurons that promote and inhibit feeding (Figure 1; Atasoy et al., 2012). Unlike other neurons involved in hunger, these cells did not appear to respond to food-predicting cues. Molecular data on the different cell types in the arcuate nucleus could be used to identify this new population, potentially revealing a new hunger-related neural mechanism (Campbell et al., 2017).
Taken together, the findings of Kim et al. reveal that eating and drinking alter the activity of AVP neurons via two distinct neural circuits (Figure 1). There are, however, a few limitations to this study. For instance, the regulation of lamina terminalis neurons and vasopressin is inseparable. Indeed, manipulation of the lamina terminalis neurons inevitably changes thirst drive, water intake and the activity of AVP neurons. This makes it difficult to pinpoint the source of predictive signals in AVP neurons.
Another question has to do with the physiological significance of the anticipatory regulation of lamina terminalis neurons and AVP neurons. If water-predicting cues suppress excitatory neurons in the lamina terminalis, how does the brain maintain the desire to drink? This issue is particularly important for the thirst system since thirst-driving neurons can have acute effects on drinking behavior (Augustine et al., 2020). It is possible that the lamina terminalis regulates thirst and vasopressin secretion through different populations of neurons. Future work could investigate if the neurons directly connected to AVP neurons are different to the ones that drive thirst. Identifying the individual components of the behavioral and hormonal response may provide new insights into how the brain regulates the uptake and excretion of fluids.
References
-
A molecular census of arcuate hypothalamus and median eminence cell typesNature Neuroscience 20:484–496.https://doi.org/10.1038/nn.4495
-
Inhibition of plasma vasopressin after drinking in dehydrated humansThe American Journal of Physiology 247:R968–R971.https://doi.org/10.1152/ajpregu.1984.247.6.R968
-
The sensory circumventricular organs of the mammalian brainAdvances in Anatomy, Embryology, and Cell Biology 172:1–122.https://doi.org/10.1007/978-3-642-55532-9
-
Satiety and inhibition of vasopressin secretion after drinking in dehydrated dogsThe American Journal of Physiology 240:E394–E401.https://doi.org/10.1152/ajpendo.1981.240.4.E394
Article and author information
Author details
Publication history
- Version of Record published: November 18, 2021 (version 1)
Copyright
© 2021, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 968
- views
-
- 123
- downloads
-
- 2
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Vasopressin: Predicting changes in osmolality
eLife 10:e74551.
https://doi.org/10.7554/eLife.74551
Further reading
-
- Medicine
- Neuroscience
Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are >100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP’s structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.
-
- Medicine
Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.
