1.A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii.
Hongxiao YU ; Luo SHI ; Jinting CHEN ; Shirui JUN ; Yinchao HAO ; Shuang WANG ; Congrui FU ; Xiang ZHANG ; Haiyan LU ; Sheng WANG ; Fang YUAN
Neuroscience Bulletin 2022;38(2):149-165
Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTSLepRb) neurons notably activated breathing. Moreover, stimulation of NTSLepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTSLepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTSLepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca2+ transients in most NTSLepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology*
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Membrane Potentials
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Neurons/metabolism*
;
Solitary Nucleus/metabolism*
2.Circuit-Specific Control of Blood Pressure by PNMT-Expressing Nucleus Tractus Solitarii Neurons.
Shirui JUN ; Xianhong OU ; Luo SHI ; Hongxiao YU ; Tianjiao DENG ; Jinting CHEN ; Xiaojun NIE ; Yinchao HAO ; Yishuo SHI ; Wei LIU ; Yanming TIAN ; Sheng WANG ; Fang YUAN
Neuroscience Bulletin 2023;39(8):1193-1209
The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTSPNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTSPNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTSPNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTSPNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTSPNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTSPNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism*
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Blood Pressure/physiology*
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Phenylethanolamine N-Methyltransferase/metabolism*
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Neurons/metabolism*
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Paraventricular Hypothalamic Nucleus/metabolism*
3.C-fos expression within PVN and NTS of the rat induced by gastric ischemia/reperfusion injury.
Yong-Mei ZHANG ; Jian-Fu ZHANG ; You-Ting CHEN ; Chang-Dong YAN ; Xiu-Ping ZHOU
Chinese Journal of Applied Physiology 2004;20(1):20-23
AIMTo investigate the effect of paraventricular nucleus (PVN) stimulation and the c-fos expression within PVN and nucleus tractus solitarius (NTS) of the rat following gastric ischemia/reperfusion injury (GI/RI).
METHODSThe rat celiac artery was clamped for thirty minutes and reperfused for sixty minutes, using Fos immunohistochemical method (ABC method) examined the c-fos expression within PVN and NTS.
RESULTS(1) Both electrical and chemical stimulation of the PVN obviously attenuated the GI/ RI. (2) Bilateral electrolytic lesion of NTS could eliminate the protective effect of electrical stimulation of the PVN. (3) The Fos-like immunoreactive neurons were increased in bilateral PVN and NTS by GI/RI.
CONCLUSIONThe function of PVN and NTS could be affected by the GI/RI noxious stimulation. PVN, NTS were involved in the regulation of GI/RI.
Animals ; Gastric Mucosa ; pathology ; Male ; Paraventricular Hypothalamic Nucleus ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; Solitary Nucleus ; metabolism ; Stomach ; blood supply
4.Histaminergic receptor in the NTS involved in inhibition of carotid baroreflex induced by intracerebroventricular injection of HA in rats.
Guo-qing WANG ; Xi-ping ZHOU ; Xin-e SHEN
Chinese Journal of Applied Physiology 2004;20(3):285-289
AIMTo explore the role of histaminergic receptors in the nucleus tractus solitarius (NTS) in the responses of carotid baroreflex (CBR) performance to the intracerebroventricular (ICV) injection of histamine (HA).
METHODSThe left and right carotid sinus regions were isolated from the systemic circulation in 18 Wistar rats anesthetized with pentobarbital sodium. The intracarotid sinus pressure (ISP) was altered in a stepwise manner. ISP-mean arterial pressure (MAP) relationship curve and its characteristic parameters were constructed by fitting to the logistic function with five parameters. We observed the changes in CBR performance induced by ICV HA and the effects of pretreatment with HA receptors antagonists into the NTS on the responses of CBR to HA.
RESULTSICV injection of HA (100 ng) significantly shifted the ISP-MAP relationship curve upwards and moved the middle part of ISP Gain relationship curve downwards, and reduced the MAP range and maximum gain (Gmax), but increased the threshold pressure (TP), saturation pressure(SP) and ISP at Gmax (ISP(Gmax)). The pretreatment with H1 or H2 receptors antagonist, chlorpheniramine (CHL, 0.5 microg) or cimetidine (CIM, 1.5 microg) into the NTS, could obviously diminish the above-mentioned changes in CBR performance induced by HA, but the effect of CIM was less remarkable than that of CHL.
CONCLUSIONThe intracerebroventricular administration of HA results in a rapid resetting of CBR and a decrease in reflex sensitivity, and the histaminergic receptors in the NTS (H1 and H2 receptors), especially H1 receptors might play an important role in the responses of CBR to HA, and furthermore, the effects of the central HA on CBR might be related to a histaminergic descending pathway from the hypothalamus to NTS.
Animals ; Baroreflex ; drug effects ; Carotid Sinus ; drug effects ; Cerebral Ventricles ; Histamine ; pharmacology ; Male ; Rats ; Rats, Wistar ; Receptors, Histamine ; metabolism ; Solitary Nucleus ; drug effects
5.Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii.
Na LI ; Yue GUAN ; Yan-Ming TIAN ; Hui-Jie MA ; Xiangjian ZHANG ; Yi ZHANG ; Sheng WANG
Neuroscience Bulletin 2019;35(1):79-90
Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.
Animals
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Baroreflex
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physiology
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Blood Pressure
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drug effects
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Hypertension
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metabolism
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Hypoxia
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chemically induced
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Kidney
;
drug effects
;
metabolism
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Male
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Nitric Oxide Synthase Type I
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drug effects
;
metabolism
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Rats, Sprague-Dawley
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Solitary Nucleus
;
metabolism
6.The expression of GABA(A) receptor alpha1 and GABA(B) receptor 1 in medulla oblongata solitary nucleus and ambiguous nucleus in the cases of tramadol intoxication.
Shu ZHANG ; Da-Wei GUAN ; Ling WANG ; Hua-Xin WANG ; Guo-Hua ZHANG ; Rui ZHAO ; Yan-Yan FAN
Journal of Forensic Medicine 2011;27(6):401-404
OBJECTIVE:
To observe the expression of GABA(A) receptor alpha1 (GABA(A)alpha1) and GABA(B) receptor 1 (GABA(B)1) in human medulla oblongata solitary nucleus and ambiguous nucleus due to tramadol-induced death.
METHODS:
GABA(A)alpha1 and GABA(B)1 were detected by immunohistochemical SP method in tramadol-induced death group and control group. All results were evaluated by images analysis system.
RESULTS:
Low expression of GABA(A)alpha1 and GABA(B)1 were detected in solitary nucleus and ambiguous nucleus in the control brain tissue. In cases of tramadol-induced death, the expression of GABA(A)alpha1 and GABA(B)1 significantly increased.
CONCLUSION
The mechanism of tramadol intoxication death could be caused by respiratory depression induced by over-expression of GABA(A)alpha1 and GABA(B)1 in medulla oblongata solitary nucleus and ambiguous nucleus.
Adult
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Analgesics, Opioid/poisoning*
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Autopsy
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Case-Control Studies
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Cause of Death
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Female
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Forensic Toxicology
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Humans
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Immunohistochemistry
;
Male
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Medulla Oblongata/metabolism*
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Receptors, GABA-A/metabolism*
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Receptors, GABA-B/metabolism*
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Respiration Disorders/etiology*
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Solitary Nucleus/metabolism*
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Staining and Labeling
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Tramadol/poisoning*
7.Intragastric gavage with denatonium benzoate acutely induces neuronal activation in the solitary tract nucleus via the vagal afferent pathway.
Hyo Young JUNG ; Woosuk KIM ; Dae Young YOO ; Sung Min NAM ; Jong Whi KIM ; Jung Hoon CHOI ; Yeo Sung YOON ; Hye Young KIM ; In Koo HWANG
Journal of Veterinary Science 2014;15(4):459-464
Natural toxic substances have a bitter taste and their ingestion sends signals to the brain leading to aversive oral sensations. In the present study, we investigated chronological changes in c-Fos immunoreactivity in the nucleus tractus solitarius (NTS) to study the bitter taste reaction time of neurons in the NTS. Equal volumes (0.5 mL) of denatonium benzoate (DB), a bitter tastant, or its vehicle (distilled water) were administered to rats intragastrically. The rats were sacrificed at 0, 0.5, 1, 2, 4, 8, or 16 h after treatment. In the vehicle-treated group, the number of c-Fos-positive nuclei started to increase 0.5 h after treatment and peaked 2 h after gavage. In contrast, the number of c-Fos-positive nuclei in the DB-treated group significantly increased 1 h after gavage. Thereafter, the number of c-Fos immunoreactive nuclei decreased over time. The number of c-Fos immunoreactive nuclei in the NTS was also increased in a dose-dependent manner 1 h after gavage. Subdiaphragmatic vagotomy significantly decreased DB-induced neuronal activation in the NTS. These results suggest that intragastric DB increases neuronal c-Fos expression in the NTS 1 h after gavage and this effect is mediated by vagal afferent fibers.
Adjuvants, Immunologic/pharmacology
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Afferent Pathways/physiology
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Animals
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Injections/veterinary
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Ligands
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Male
;
Proto-Oncogene Proteins c-fos/*metabolism
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Quaternary Ammonium Compounds/*pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, G-Protein-Coupled/*metabolism
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Solitary Nucleus/*physiology
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Vagus Nerve/*drug effects/*physiology
8.Intracerebroventricular administration of adrenomedullin increases the expression of c-fos and activates nitric oxide-producing neurons in rat cardiovascular related brain nuclei.
Shu-Mei JI ; Ze-Min WANG ; Xue-Ping LI ; Rui-Rong HE
Acta Physiologica Sinica 2004;56(3):328-334
To define the action sites of adrenomedullin (ADM) in the rat brain, and to examine whether neuronal NO may participate in the actions of ADM, the present study was undertaken to examine the effects of i.c.v. administration of ADM on the induction of Fos protein and on nitric oxide-producing neurons in rat brain nuclei involved in cardiovascular regulation, using double immunohistochemical method for Fos and neuronal nitric oxide synthase (nNOS). Following i.c.v. administration of ADM (1 nmol/kg, 3 nmol/kg), Fos-like immunoreactivity neurons were markedly increased in several brain areas of the rat, including the nucleus of the solitary tract (NTS), the area postrema, the locus coeruleus, the parabrachial nucleus and the nucleus paragigantocelluaris laterialis (PGL) in the brainstem, the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the ventromedial hypothalamic nucleus in the hypothalamus, as well as the central amygdaloid nucleus and the lateral habenular nucleus in the forebrain. Following i.c.v. injection of ADM (1 nmol/kg, 3 nmol/kg), the number of double-labeled neurons for Fos and nNOS was increased in the PVN and SON. Small numbers of double-labeled neurons were also found in the NTS and PGL following i.c.v. injection of ADM (3 nmol/kg), while i.c.v. injection of ADM (1 nmol/kg) did not change the number of double-labeled neurons in the NTS and PGL. Pretreatment with calcitonin gene-related peptide receptor antagonist CGRP(8-37) (30 nmol/kg) significantly reduced the action of ADM (3 nmol/kg) in the brain. These results suggest that centrally administered ADM may increase the expression of c-fos in the forebrain, the hypothalamus and the brainstem and activate nitric oxide-producing neurons in the PVN, SON, NTS and PGL. These effects may be partly mediated by CGRP receptors.
Adrenomedullin
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Animals
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Brain Stem
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metabolism
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Injections, Intraventricular
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Male
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Nitric Oxide
;
metabolism
;
Nitric Oxide Synthase Type I
;
metabolism
;
Paraventricular Hypothalamic Nucleus
;
metabolism
;
Peptides
;
pharmacology
;
Proto-Oncogene Proteins c-fos
;
biosynthesis
;
genetics
;
Rats
;
Rats, Sprague-Dawley
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Receptors, Calcitonin Gene-Related Peptide
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antagonists & inhibitors
;
physiology
;
Solitary Nucleus
;
physiology
9.Glutaminergic neurons expressing c-Fos in the brainstem and amygdala participate in signal transmission and integration of sweet taste.
Xiao-lin ZHAO ; Jian-qun YAN ; Ke CHEN ; Xue-juan YANG ; Jin-rong LI ; Yuan ZHANG
Journal of Southern Medical University 2011;31(7):1138-1141
OBJECTIVETo examine the role of glutaminergic neurons in the transmission and integration of the sweat taste information in the brain stem and the amygdala.
METHODSConscious Sprague-Dawley rats were subjected to oral sweet taste or water (control) stimulations. The activated neurons were identified by detecting c-Fos expression in taste-related brain areas, and the glutaminergic neurons by detecting vesicular glutamate transpoter-3 (VGLUT3).
RESULTSCompared with control group, the rats with oral sucrose solution stimulation exhibited significantly increased c-Fos-expressing and double-labeled neurons in the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN) and the amygdala.
CONCLUSIONNeurons in the NST, PBN and amygdala are activated after oral sweet taste stimulation. The sweet taste perception at different levels in the CNS is partly mediated by glutamate.
Amygdala ; physiology ; Animals ; Brain Stem ; physiology ; Glutamic Acid ; metabolism ; Male ; Neurons ; metabolism ; physiology ; Proto-Oncogene Proteins c-fos ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Solitary Nucleus ; cytology ; physiology ; Sucrose ; administration & dosage ; metabolism ; Taste Perception ; physiology ; Vesicular Glutamate Transport Proteins ; metabolism