Fig 1 - uploaded by Laura Vivas
Content may be subject to copyright.
Schematic representation of the locus coeruleus (LC) and granular insular cortex (GI) nuclei showing the specific areas that were evaluated in the analysis of Fos and Fos- FG immunoreactive pattern.
Source publication
Modulation of salt appetite involves interactions between the circumventricular organs (CVOs) receptive areas and inhibitory hindbrain serotonergic circuits. Recent studies provide support to the idea that the serotonin action in the lateral parabrachial nucleus (LPBN) plays an important inhibitory role in the modulation of sodium appetite. The aim...
Contexts in source publication
Context 1
... all nuclei were counted at one level. The distance from the bregma of the corresponding plates is indicated between brackets: hypothalamic paraventricular nucleus (PVN, − 1.8 mm), central amygdaloid nucleus (CeA, − 2.3 mm), bed nucleus of the stria terminalis, lateral division, dorsal part (BSTLD, − 0.26 mm) (Fig. 8), granular insular cortex (GI) (Fig. 1), subfornical organ (SFO, −0.92 mm), organum vasculosum of the lamina terminalis (OVLT, −0.11 mm) (Fig. 6), dorsal raphe nucleus (DRN, − 8.00 mm) (Fig. 6), locus coeruleus (LC, −10.04 mm) (Fig. 1), the nucleus of the solitary tract adjacent to area postrema (NTS/AP, − 13.68 mm) (Fig. ...
Context 2
... nucleus (CeA, − 2.3 mm), bed nucleus of the stria terminalis, lateral division, dorsal part (BSTLD, − 0.26 mm) (Fig. 8), granular insular cortex (GI) (Fig. 1), subfornical organ (SFO, −0.92 mm), organum vasculosum of the lamina terminalis (OVLT, −0.11 mm) (Fig. 6), dorsal raphe nucleus (DRN, − 8.00 mm) (Fig. 6), locus coeruleus (LC, −10.04 mm) (Fig. 1), the nucleus of the solitary tract adjacent to area postrema (NTS/AP, − 13.68 mm) (Fig. ...
Context 3
... (p = 0.001) and the DRN (p = 0.01) of the PD group, as previously shown (Franchini & Vivas, 1999;Franchini et al., 2002;Godino et al., 2007). In contrast, along the LC nucleus, we did not find any significant difference between the number of cells immunoreactive for Fos (p = 0.43) or Fos-FG (p = 0.55), comparing control and dialyzed animals (see Fig. ...
Context 4
... granular insular cortex (GI) previously associated with the regulation of ingestive behaviors also showed an increased number of Fos cells in the PD group (Fos: p = 0.006); however the number of double immunoreactive neurons Fos-FG tended to increase but did not reach significant levels (Fos-FG: p = 0.09) (Figs. 1 and 7). ...
Citations
... ANP administered into the third ventricle of sodium-deplete rats attenuated salt intake [142,143]. Like oxytocin, increased ANP plasma levels are associated with sodium appetite satiety [144]. ...
Sodium (Na+) is crucial for numerous homeostatic processes in the body and, consequentially, its levels are tightly regulated by multiple organ systems. Sodium is acquired from the diet, commonly in the form of NaCl (table salt), and substances that contain sodium taste salty and are innately palatable at concentrations that are advantageous to physiological homeostasis. The importance of sodium homeostasis is reflected by sodium appetite, an “all-hands-on-deck” response involving the brain, multiple peripheral organ systems, and endocrine factors, to increase sodium intake and replenish sodium levels in times of depletion. Visceral sensory information and endocrine signals are integrated by the brain to regulate sodium intake. Dysregulation of the systems involved can lead to sodium overconsumption, which numerous studies have considered causal for the development of diseases, such as hypertension. The purpose here is to consider the inverse—how disease impacts sodium intake, with a focus on stress-related and cardiometabolic diseases. Our proposition is that such diseases contribute to an increase in sodium intake, potentially eliciting a vicious cycle toward disease exacerbation. First, we describe the mechanism(s) that regulate each of these processes independently. Then, we highlight the points of overlap and integration of these processes. We propose that the analogous neural circuitry involved in regulating sodium intake and blood pressure, at least in part, underlies the reciprocal relationship between neural control of these functions. Finally, we conclude with a discussion on how stress-related and cardiometabolic diseases influence these circuitries to alter the consumption of sodium.
... In this regard, a decisive role has been described for serotoninergic pathways that project from the AP to the lateral parabrachial nucleus (lPBN) [78]. In this way, pharmacological blockade by the intraparabrachial administration of 5-HT antagonists was found to increase Na consumption [79][80][81][82][83][84][85][86]. Other afferents to the lPBN derive from the rNST. ...
Body sodium (Na) levels must be maintained within a narrow range for the correct functioning of the organism (Na homeostasis). Na disorders include not only elevated levels of this so-lute (hypernatremia), as in diabetes insipidus, but also reduced levels (hyponatremia), as in cerebral salt wasting syndrome. The balance in body Na levels therefore requires a delicate equilibrium to be maintained between the ingestion and excretion of Na. Salt (NaCl) intake is processed by receptors in the tongue and digestive system, which transmit the information to the nucleus of the solitary tract via a neural pathway (chorda tympani/vagus nerves) and to circumventricular organs, including the subfornical organ and area postrema, via a humoral pathway (blood/cerebrospinal fluid). Circuits are formed that stimulate or inhibit homeostatic Na intake involving participation of the parabrachial nucleus, pre-locus coeruleus, medial tuberomammillary nuclei, median eminence, par-aventricular and supraoptic nuclei, and other structures with reward properties such as the bed nucleus of the stria terminalis, central amygdala, and ventral tegmental area. Finally, the kidney uses neural signals (e.g., renal sympathetic nerves) and vascular (e.g., renal perfusion pressure) and humoral (e.g., renin-angiotensin-aldosterone system, cardiac natriuretic peptides, antidiuretic hormone , and oxytocin) factors to promote Na excretion or retention and thereby maintain extracellular fluid volume. All these intake and excretion processes are modulated by chemical messengers, many of which (e.g., aldosterone, angiotensin II, and oxytocin) have effects that are coordinated at peripheral and central level to ensure Na homeostasis.
... On the other hand, this excitatory pathway is typically limited by inhibitory hindbrain serotonergic (5-HT) and hypothalamic oxytocin (OXT) circuits 6,7,9,10,27-31 . We have detailed a specific 5-HT pathway [that includes the dorsal raphe nucleus (DRN, containing serotonergic neurons) and the lateral parabrachial nucleus (LPBN, the site of 5-HT action)] involved in the signaling of the satiation process of sodiumdepletion-induced sodium appetite after sodium consumption that occurs 24 h after sodium depletion 6,10,11,27,31 . The OXT neural activity of supraoptic and paraventricular cells (SON and PVN, respectively) is implicated in the hypertonicity signaling after induced sodium intake (24 h after sodium depletion) since these are intrinsically osmosensors due to the presence of transient receptor potential channel 1 (TRPV1), like OVLT and SFO circumventricular organs (CVOs) 27,32 . ...
... Considering the neuroanatomical and physiological 5-HT connection from the DRN to the SFO and AV3V, where sodium appetite is stimulated, and the LPBN, where sodium appetite is inhibited 6,10,11,43 , and the presence of serotonin 2A (5-HT 2A ) and 2C (5-HT 2C ) receptors in these areas 44 , we analyzed the temporal effect of SD on Htr2c and Htr2a expression. At the LPBN we observed a significant decrease in the expression of Htr2c mRNA after SD [sodium condition (CD vs SD) main effect: F 1.10 = 18.29; p = 0.002; η2p = 0.44 Fig. 4f]. ...
... Several studies postulated an inhibitory role of 5-HT on sodium appetite, with the LPBN as the main structure involved in this effect 6,11,[27][28][29]31,34,58 . The pharmacological antagonism of 5-HT 2C/2A in the LPBN increases SA even as early as two hours after SD when SA is inapparent 6,29 . ...
Sodium appetite is a motivational state involving homeostatic behavior, seeking the ingest of salty substances after sodium loss. There is a temporal dissociation between sodium depletion (SD) and the appearance of sodium appetite. However, the responsible mechanisms for this delay remain poorly elucidated. In the present study, we measured the temporal changes at two and 24 h after SD in the gene expression of key elements within excitatory, inhibitory, and sensory areas implicated in the signaling pathways involved in the onset of sodium appetite. In SD rats, we observed that the expression of critical components within the brain control circuit of sodium appetite, including Angiotensin-type-1 receptor (Agtr1a), Oxytocin-(OXT-NP)-neurophysin-I, and serotonergic-(5HT)-type-2c receptor (Htr2c) were modulated by SD, regardless of time. However, we observed reduced phosphorylation of mitogen-activated protein kinases (MAPK) at the paraventricular nucleus (PVN) and increased oxytocin receptor (Oxtr) mRNA expression at the anteroventral of the third ventricle area (AV3V), at two hours after SD, when sodium appetite is inapparent. At twenty-four hours after SD, when sodium appetite is released, we observed a reduction in the mRNA expression of the transient receptor potential channel 1gene (Trpv1) and Oxtr in the AV3V and the dorsal raphe nucleus, respectively. The results indicate that SD exerts a coordinated timing effect, promoting the appearance of sodium appetite through changes in MAPK activity and lower Trpv1 channel and Oxtr expression that trigger sodium consumption to reestablish the hydroelectrolytic homeostasis.
... Another key site is the parabrachial nucleus, where oxytocin receptor-expressing neurones have been implicated in the regulation of water and saline intake (111,112). ...
In the rat supraoptic nucleus, every oxytocin cell projects to the posterior pituitary, and is involved in both reflex milk ejection during lactation, and in regulating uterine contractions during parturition. All are also osmosensitive, regulating natriuresis. All are also regulated by signals that control appetite, including neural and hormonal signals that arise from the gut after food intake and from the sites of energy storage. All are also involved in sexual behaviour, anxiety‐related behaviours, and social behaviours. The challenge is to understand how a single population of neurones can coherently regulate such a diverse set of functions, and adapt to changing physiological states. Their multiple functions arise from complex intrinsic properties which confer sensitivity to a wide range of internal and environmental signals. Many of these properties have a distant evolutionary origin, in multi‐functional, multisensory neurones of Urbilateria, the hypothesised common ancestor of vertebrates, insects and worms. Their properties allow different patterns of oxytocin release into the circulation from their axon terminals in the posterior pituitary, into other brain areas from axonal projections, and independent release from their dendrites.
This article is protected by copyright. All rights reserved.
... Moreover, the medioventral septal (MVS) nuclei might play a role in the axoplasmic transport of VP [23,24]. Other brain nuclei involved in VP secretion are the amygdala [25,26], the locus coeruleus [27,28], the dorsal raphe nuclei (DRN) [29][30][31][32][33][34], the retrotrapezoid nucleus of the rostroventral medulla oblungata [35][36][37], the lateral parabrachial nucleus (LPBN) [38,39], the diagonal band of Broca (DBB) [40][41][42][43] and the bed nucleus of the stria terminalis (BST) [44,45]. Therefore the synapses that these afferent neural pathways form on MCNs of SON and PVN use several neurotransmitters and neuropeptides that activate ligandgated ion channels and G protein coupled receptors (GPCRs), in order to modulate VP or OT release. ...
... In addition, 5-HT and drugs enhancing 5-HT neurotransmission stimulate VP and OT secretion [32,97,112]. Godino and coworkers [39] showed, after sodium intake, c-Fos immunoreactivity in neurons along the PVN, amygdala, NTS and CVOs having direct connections with LPBN. Therefore, the LPBN via 5-HTergic synaptic connections with brain areas involved in the control of the osmolality of the extracellular fluid and blood volume is part of central circuitry subserving salt-water balance. ...
Background:
Magnocellular neurosecretory neurons of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei synthesize vasopressin and oxytocin in response to signals generated by osmoreceptors and baroreceptors and, respectively, by receptors of the nipples and cervix.
Methods:
We analyzed the literature identifying relevant articles dealing with synaptic inputs of neural afferent pathways to Vasopressin-and Oxytocin-secreting neurons of SON and PVN.
Results:
This article focuses on the multisynaptic pathways involved in the regulation of Vasopressin and Oxytocin secretion.
Conclusion:
An updated topographic description of the afferent pathways involved in the regulation of VPergic and OTergic neurons and their synaptic inputs inducing the stimulus-secretion-coupling has been depicted.
... Inhibition of salt appetite is associated with inhibitory action of serotonin from dorsal raphe neurons released in the lateral parabrachial nucleus (lPB), which is a key node in a regulatory network involving brain stem and forebrain structures, including lamina terminalis components. 110 It is not clear whether the lPB is a site of oxytocin action. ...
During pregnancy multiple physiological adaptations take place in the mother to optimize the chances of a successful pregnancy outcome. These adaptations play a critical role in reproductive physiology, serving to (1) increase the supply of oxygen and nutrients to the placenta and maternal organs supporting the pregnancy; (2) optimize fetal growth and development; (3) prepare expanded oxytocin stores for when they are in demand at parturition and for lactation; (4) protect the pregnancy from premature birth; (5) protect the fetus from adverse programming, e.g., by maternal stress; (6) ensure adequate milk production and delivery at lactation; and (7) ensure that the appropriate brain circuits are primed and behaviors altered to deliver sufficient maternal care after parturition. In this chapter we focus on these pregnancy-related adaptations that are organized by the maternal brain, many of which are induced by the increased levels of pregnancy hormones.
... Several lines of evidence converge to suggest a circuit formed by LPBN, NTS and AP coupled to Acb, CeA, parvocellular PVN and lamina terminalis [8,[12][13][14]22,23,[28][29][30][31][32]39,40]. The present work mapped brain Fos-ir associated with that circuit and WD-PR. ...
... This implies that CSF-CN might be producing an inhibitory signal for inducing sodium satiety in the LPBN, but not in the SFO and OVLT. There is a function connection between CSF-CN and LPBN, while the anatomical connections could be direct or indirect, via the DRN to the LPBN [19,56], but whether the connection is direct or indirect between CSF-CN and LPBN needsfurther research. ...
... We have previously shown in male rats that the main changes in c-fos expression along these nuclei are evident after sodium consumption induced by sodium depletion, suggesting they may form a circuit subserving sodium balance regulation. These data are consistent with previous lesion, pharmacological, and physiological studies showing these nuclei are components of a inhibitory circuit modulating sodium intake (15,27,28,41,49). Although the present results confirm previous data showing a sodium-depletion induced FOS-ir along these nuclei during the appetitive phase of sodium appetite, they are also demonstrating for the first time that XX SCC mice have increased neural activity within these nuclei and above all a major basal activity in XX SCC individuals. ...
Previous studies indicate a sex chromosome complement (SCC) effect on the Angiotensin II-sexually dimorphic hypertensive and bradycardic baroreflex responses. We sought to evaluate whether SCC may differentially modulate sexually dimorphic induced sodium appetite and specific brain activity due to physiological stimulation of the rennin angiotensin system. For this purpose, we used the "four core genotypes" mouse model, in which the effect of gonadal sex and SCC is dissociated, allowing comparisons of sexually dimorphic traits between XX and XY females as well as in XX and XY males. Gonadectomized mice were sodium depleted by furosemide (50 mg/kg) and low sodium diet treatment; control groups were administered the vehicle and maintained on normal sodium diet. Twenty-one hours later, the mice were divided into two groups: one was submitted to the water/NaCl 2% choice intake test, while the other was perfused and their brains subjected to the Fos-immunoreactivity (Fos-ir) procedure. Sodium depletion, regardless of genetic sex (XX or XY), induced a significantly lower sodium and water intake in females than in males, confirming the existence in mice of sexual dimorphism in sodium appetite and the organizational involvement of gonadal steroids. Moreover, our results demonstrate a SCC effect on induced brain Fos-ir, showing increased brain activity in XX-SCC mice at the paraventricular nucleus, nucleus of the solitary tract and lateral parabrachial nucleus, as well as an XX-SCC augmented effect on sodium-depletion induced brain activity at two circumventricular organs, the subfornical organ and area postrema, nuclei closely involved in fluid and blood pressure homeostasis.
... The cerebral structures involved in controlling the excitatory appetitive and inhibitory or satiety phases of sodium intake are likely to be interconnected with one another, constituting a neural network that integrates associated information (Fitzsimons 1998;Johnson and Thunhorst 2007). Our previous evidence indicates that modulation of salt appetite involves interactions between the CVO receptive areas and inhibitory hindbrain serotonergic circuits (Figures 9.1 and 9.2) (Badauê-Passos et al. 2007;Godino et al. 2007Godino et al. , 2010. That is, for normal sodium appetite sensation, and consequently for appropriate salt drinking after sodium depletion, the Downloaded by [Laura Vivas] at 11:29 18 October 2013 hyponatremia and the released ANG II should act centrally both to activate brain osmo-sodium and angiotensinergic receptors that stimulate salt appetite, and also to inhibit inhibitory brain 5-HT mechanisms, thus removing a "braking" mechanism. ...
... Our recent connectional studies using retrograde tracers in sodium-depleted rats ingesting salt suggest that structures of the LT inform the DRN and LPBN of sodium status or sodium consumption, and/or of volume expansion by a descending neural pathway. In this way, cells within the LT may contribute to inhibitory mechanisms involving 5-HT neurons in the DRN and the release of 5-HT within the LPBN, which limit the intake of sodium and prevent excess expansion of extracellular volume (Badauê-Passos et al. 2007;Godino et al. 2010;Margatho et al. 2008). In these morphofunctional studies using the retrograde tracer, fluorogold (FG), with Fos we found significantly increased numbers of Fos-FG double-immunolabeled neurons in the LT and several other brain areas previously involved in the control of water and saline drinking and excretion after fluid depletion (Badaue-Passos et al. 2007;Godino et al. 2010). ...
... In this way, cells within the LT may contribute to inhibitory mechanisms involving 5-HT neurons in the DRN and the release of 5-HT within the LPBN, which limit the intake of sodium and prevent excess expansion of extracellular volume (Badauê-Passos et al. 2007;Godino et al. 2010;Margatho et al. 2008). In these morphofunctional studies using the retrograde tracer, fluorogold (FG), with Fos we found significantly increased numbers of Fos-FG double-immunolabeled neurons in the LT and several other brain areas previously involved in the control of water and saline drinking and excretion after fluid depletion (Badaue-Passos et al. 2007;Godino et al. 2010). In these studies, the retrograde tracer was injected into the DRN or the LPBN approximately 10 days before sodium depletion experiments. ...
