Distinct neural mechanisms for the control of thirst and salt appetite in the subfornical organ

Matsuda, Takashi; Hiyama, Takeshi Y.; Niimura, Fumio; Matsusaka, Taiji; Fukamizu, Akiyoshi; Kobayashi, Kenta; Kobayashi, Kazuto; Noda, Masaharu

doi:10.1038/nn.4463

Cited by 141 publications

(221 citation statements)

References 71 publications

(91 reference statements)

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“…Mice were placed individually in lickometer cages equipped with two bottles; one filled with 3% NaCl and the other with H 2 O. Furosemide diuresis markedly increased consumption of 3% NaCl in controls, while sodium appetite was mostly absent in mice lacking ~65% of their NTS HSD2 neurons (Figure 5D–F). Diminished 3% NaCl ingestion in ablated mice also lead to a small decrease in H 2 O drinking compared to controls – a result also observed by others (Matsuda et al, 2017). In yet another model of Na + deficiency, we assessed sodium appetite in Na + -deprived mice fed only low-sodium diet.…”

Section: Resultssupporting

confidence: 84%

“…With this in mind, it is of interest that sodium appetite involves synergy between ATII and aldosterone (Epstein, 1992). ATII and aldosterone signaling are both critical for deficiency-induced appetite (Matsuda et al, 2017; Sakai et al, 1986), and, in non-depleted animals, sodium appetite is synergistically induced by simultaneous administration of ATII and mineralocorticoids (Fluharty and Epstein, 1983). This synergy between ATII and aldosterone in appetite likely allows for smaller deficiencies of Na + to stimulate appetite – hence, preemptively warding off larger disturbances and their adverse circulatory consequences (Sakai et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

“…Supporting this, SFO-specific knockout of AT1aRs suppresses Na + intake induced by Na + deficiency. Likewise, inhibition of VGLUT2-expressing SFO neurons that project to the ventral bed nucleus of the stria terminalis (vBNST) eliminates sodium appetite (Matsuda et al, 2017). These data strongly suggest the existence of glutamatergic ATII-sensitive SFO neurons that regulate sodium appetite via projections to the vBNST.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling

Resch

Fenselau

Madara

et al. 2017

Neuron

109

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Summary Sodium deficiency increases angiotensin II (ATII) and aldosterone, synergistically stimulating its retention and consumption. Recently, ATII-responsive neurons in the subfornical organ (SFO) and aldosterone-sensitive neurons in the nucleus of the solitary tract (NTSHSD2 neurons) were shown to drive sodium appetite. Here we investigate the basis for NTSHSD2 neuron activation, identify the circuit by which NTSHSD2 neurons drive appetite, and uncover an interaction between the NTSHSD2 circuit and ATII signaling. NTSHSD2 neurons respond to sodium deficiency with spontaneous pacemaker-like activity – the consequence of "cardiac" HCN and Nav1.5 channels. Remarkably, NTSHSD2 neurons are necessary for sodium appetite, and with concurrent ATII signaling their activity is sufficient to produce rapid consumption. Importantly, NTSHSD2 neurons stimulate appetite via projections to the vlBNST, which is also the effector site for ATII-responsive SFO neurons. The interaction between angiotensin signaling and NTSHSD2 neurons provides a neuronal context for the long-standing "synergy hypothesis" of sodium appetite regulation.

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Section: Resultssupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling

Resch

Fenselau

Madara

et al. 2017

Neuron

109

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“…SFO nNOS neurons project their axons to other nuclei of the lamina terminalis (OVLT and MnPO) 10,25 , as well as to the paraventricular and supraoptic nuclei, which contain vasopressin-expressing neurons 19 . These axonal projections and the downstream neurons define a framework of circuit elements that control thirst-related behaviours and hormonal outputs 26 .…”

Section: Hierarchical Circuit For Thirstmentioning

confidence: 99%

Hierarchical neural architecture underlying thirst regulation

Augustine

Gökçe

Lee

et al. 2018

Nature

121

139

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Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance.

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“…Numerous studies, most recently optogenetics have implicated the subfornical organ (SFO) as an important regulator of fluid intake. 23,24 Water deprivation increases neural activity in the SFO, along with other structures in the lamina terminalis. 25 We previously showed that increased synthesis of Ang-II specifically in the SFO is sufficient to induce water intake.…”

Section: Discussionmentioning

confidence: 99%

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism

et al. 2017

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The brain specific isoform of renin (Ren-b), has been proposed as a negative regulator of the brain renin-angiotensin system (RAS). We analyzed mice with a selective deletion of Ren-b which preserved expression of the classical renin (Ren-a) isoform. We reported that Ren-bNull mice exhibited central RAS activation and hypertension through increased expression of Ren-a, but the dipsogenic and metabolic effects in Ren-bNull mice are unknown. Fluid intake was similar in control and Ren-bNull mice at baseline and both exhibited an equivalent dipsogenic response to DOCA-salt. Dehydration promoted increased water intake in Ren-bNull mice, particularly after DOCA-salt. Ren-bNull and control mice exhibited similar body weight when fed a chow diet. However, when fed a high fat diet, male Ren-bNull mice gained significantly less weight than control mice, an effect blunted in females. This difference was not due to changes in food intake, energy absorption or physical activity. Ren-bNull mice exhibited increased resting metabolic rate concomitant with increased uncoupled protein 1 expression and sympathetic nerve activity to the interscapular brown adipose tissue (BAT), suggesting increased thermogenesis. Ren-bNull mice were modestly intolerant to glucose and had normal insulin sensitivity. Another mouse model with markedly enhanced brain RAS activity (sRA mice) exhibited pronounced insulin sensitivity concomitant with increased BAT glucose uptake. Altogether, these data support the hypothesis that the brain RAS regulates energy homeostasis by controlling resting metabolic rate, and that Ren-b deficiency increases brain RAS activity. Thus, the relative level of expression of Ren-b and Ren-a may control activity of the brain RAS.

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Distinct neural mechanisms for the control of thirst and salt appetite in the subfornical organ

Cited by 141 publications

References 71 publications

Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling

Aldosterone-Sensing Neurons in the NTS Exhibit State-Dependent Pacemaker Activity and Drive Sodium Appetite via Synergy with Angiotensin II Signaling

Hierarchical neural architecture underlying thirst regulation

Selective Deletion of Renin-b in the Brain Alters Drinking and Metabolism

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