A gut-to-brain signal of fluid osmolarity controls thirst satiation

Zimmerman, Christopher A.; Huey, Erica L.; Ahn, Jamie S.; Beutler, Lisa R.; Tan, Chan Lek; Kosar, Seher; Bai, Lijun; Chen, Yiming; Corpuz, Timothy V; Madisen, Linda; Zeng, Hongkui; Knight, Zachary A.

doi:10.1038/s41586-019-1066-x

Cited by 100 publications

(105 citation statements)

References 57 publications

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“…Key features of this system are consistent with studies of the mammalian hypothalamus. First, neurosecretory hypothalamic neurons have been reported to rapidly respond to a variety of stressful and aversive events, including oxytocin and corticotrophin-releasing factor neurons in the paraventricular nucleus (Condés-Lara et al, 2009;Kim et al, 2019), and vasopressin neurons in the supraoptic nucleus (Zimmerman et al, 2019). In addition, electrical stimulation of the paraventricular hypothalamus in mouse evokes rapid escape behaviors (Lammers at el., 1988), and optogenetic activation of corticotrophin-releasing factor neurons drives rodents to perform context-specific motor actions (Füzesi et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Multiple overlapping hypothalamus-brainstem circuits drive rapid threat avoidance

Lovett-Barron

Chen

Bradbury

et al. 2019

Preprint

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Animals survive environmental challenges by adapting their physiology and behavior through homeostatic regulatory processes, mediated in part by specific neuropeptide release from the hypothalamus. Animals can also avoid environmental stressors within seconds, a fast behavioral adaptation for which hypothalamic involvement is not established. Using brain-wide neural activity imaging in behaving zebrafish, here we find that hypothalamic neurons are rapidly engaged during common avoidance responses elicited by various environmental stressors. By developing methods to register cellular-resolution neural dynamics to multiplexed in situ gene expression, we find that each category of stressor recruits similar combinations of multiple peptidergic cell types in the hypothalamus. Anatomical analysis and functional manipulations demonstrate that these diverse cell types play shared roles in behavior, are glutamatergic, and converge upon spinal-projecting brainstem neurons required for avoidance. These data demonstrate that hypothalamic neural populations, classically associated with slow and specific homeostatic adaptations, also together give rise to fast and generalized avoidance behavior.

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Section: Discussionmentioning

confidence: 99%

Multiple overlapping hypothalamus-brainstem circuits drive rapid threat avoidance

Lovett-Barron

Chen

Bradbury

et al. 2019

Preprint

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“…This osmosensory signal (a) involves the vagus nerve, (b) is integrated with oropharyngeal and blood-borne signals, and (c) is transmitted from the gut to forebrain neurons that control thirst and vasopressin release. [11] In the rodent brain, activation of approximately 24,000 neurons in 34 brain loci revealed a global brainwide representation of a thirst-motivated state. This state appears to moderate the propagation of sensory information and its transformation into behavioral output.…”

Section: Observations Perspectives and Paradigms A Publications Bmentioning

confidence: 99%

“…As shown in Figure 5, the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON) are important downstream targets of the lamina terminalis that control release of AVP from the posterior pituitary into the circulation. Thus, PVH signaling influences not only urine production and blood pressure, but also the autonomic responses of heart rate and natriuresis [11]. baroreceptor, plasma sodium concentration, and upper gastrointestinal tract information via the vagus nerve to the MnPO [90,92].…”

Section: Animal Research Compliments Human Brain Imagingmentioning

confidence: 99%

“…This vital stability, in a TBW pool of 44 L (i.e., 60% of 75 kg body mass), is accomplished via a complex, dynamic network of sensory nerves, brain integration, and neuroendocrine responses. Figures 1 and 2 consolidate information from multiple publications [5][6][7][8][9][10][11] and represent the dynamic complexity of human fluid-electrolyte regulation. Figure 1 summarizes the varied homeostatic responses that occur (e.g., the sensation of thirst) in response to osmotically driven intracellular dehydration (left side) and extracellular hypovolemia (right side) that includes reduced circulating blood plasma and blood pressure.…”

Section: Introductionmentioning

confidence: 98%

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Thirst and Drinking Paradigms: Evolution from Single Factor Effects to Brainwide Dynamic Networks

Armstrong

Kavouras

2019

Nutrients

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The motivation to seek and consume water is an essential component of human fluid–electrolyte homeostasis, optimal function, and health. This review describes the evolution of concepts regarding thirst and drinking behavior, made possible by magnetic resonance imaging, animal models, and novel laboratory techniques. The earliest thirst paradigms focused on single factors such as dry mouth and loss of water from tissues. By the end of the 19th century, physiologists proposed a thirst center in the brain that was verified in animals 60 years later. During the early- and mid-1900s, the influences of gastric distention, neuroendocrine responses, circulatory properties (i.e., blood pressure, volume, concentration), and the distinct effects of intracellular dehydration and extracellular hypovolemia were recognized. The majority of these studies relied on animal models and laboratory methods such as microinjection or lesioning/oblation of specific brain loci. Following a quarter century (1994–2019) of human brain imaging, current research focuses on networks of networks, with thirst and satiety conceived as hemispheric waves of neuronal activations that traverse the brain in milliseconds. Novel technologies such as chemogenetics, optogenetics, and neuropixel microelectrode arrays reveal the dynamic complexity of human thirst, as well as the roles of motivation and learning in drinking behavior.

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“…As essential aspects of optimal physiological function and human survival, intracellular and extracellular fluid concentrations and total body water are regulated by a complex, dynamic network of sensory nerves, autonomic neuroendocrine responses, and central integration at specific brain loci [1][2][3]. Intracellular dehydration, movement of extracellular water into cells, and the resulting increase of plasma osmolality which is detected by central osmosensors, modulate thirst, drinking behavior, and renal water retention (i.e., via the antidiuretic hormone arginine vasopressin) to stabilize the volume and concentration of the extracellular fluid [4,5].…”

Section: Introductionmentioning

confidence: 99%

Inputs to Thirst and Drinking during Water Restriction and Rehydration

et al. 2020

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Current models of afferent inputs to the brain, which influence body water volume and concentration via thirst and drinking behavior, have not adequately described the interactions of subconscious homeostatic regulatory responses with conscious perceptions. The purpose of this investigation was to observe the interactions of hydration change indices (i.e., plasma osmolality, body mass loss) with perceptual ratings (i.e., thirst, mouth dryness, stomach emptiness) in 18 free-living, healthy adult men (age, 23 ± 3 y; body mass, 80.09 ± 9.69 kg) who participated in a 24-h water restriction period (Days 1–2), a monitored 30-min oral rehydration session (REHY, Day 2), and a 24-h ad libitum rehydration period (Days 2–3) while conducting usual daily activities. Laboratory and field measurements spanned three mornings and included subjective perceptions (visual analog scale ratings, VAS), water intake, dietary intake, and hydration biomarkers associated with dehydration and rehydration. Results indicated that total water intake was 0.31 L/24 h on Day 1 versus 2.60 L/24 h on Day 2 (of which 1.46 L/30 min was consumed during REHY). The increase of plasma osmolality on Day 1 (297 ± 4 to 299 ± 5 mOsm/kg) concurrent with a body mass loss of 1.67 kg (2.12%) paralleled increasing VAS ratings of thirst, desire for water, and mouth dryness but not stomach emptiness. Interestingly, plasma osmolality dissociated from all perceptual ratings on Day 3, suggesting that morning thirst was predominantly non-osmotic (i.e., perceptual). These findings clarified the complex, dynamic interactions of subconscious regulatory responses with conscious perceptions during dehydration, rehydration, and reestablished euhydration.

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A gut-to-brain signal of fluid osmolarity controls thirst satiation

Cited by 100 publications

References 57 publications

Multiple overlapping hypothalamus-brainstem circuits drive rapid threat avoidance

Multiple overlapping hypothalamus-brainstem circuits drive rapid threat avoidance

Thirst and Drinking Paradigms: Evolution from Single Factor Effects to Brainwide Dynamic Networks

Inputs to Thirst and Drinking during Water Restriction and Rehydration

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