The nucleus tractus solitarius (NTS) is the primary brain region for receiving and integrating cardiovascular afferent signals. It plays a crucial role in maintaining balance of autonomic nervous system and regulating blood pressure through cardiovascular reflexes. Neurons within the NTS form complex synaptic connections and interact reciprocally with other brain regions. The NTS regulates autonomic nervous system activity and arterial blood pressure through modulating baroreflex, sympathetic nerve activity, renin-angiotensin-aldosterone system, and oxidative stress. Dysfunctions in NTS activity may contribute to hypertension. Understanding the NTS' role in centrally regulating blood pressure and alterations of neurotransmission or signaling pathways in the NTS may provide rationale for new therapeutic strategies of prevention and treatment. This review summarizes the research findings on autonomic nervous system regulation and arterial blood pressure control by NTS, as well as unresolved questions, in order to provide reference for future investigation.
Solitary Nucleus/physiopathology* ; Hypertension/physiopathology* ; Humans ; Animals ; Autonomic Nervous System/physiopathology* ; Blood Pressure/physiology* ; Baroreflex/physiology* ; Renin-Angiotensin System/physiology* ; Sympathetic Nervous System/physiology*

The central amygdala (CeA) is a crucial modulator of emotional, behavioral, and autonomic functions, including cardiovascular responses. Despite its importance, the specific circuit by which the CeA modulates blood pressure remains insufficiently explored. Our investigations demonstrate that photostimulation of GABAergic neurons in the centromedial amygdala (CeM^GABA), as opposed to those in the centrolateral amygdala (CeL), produces a depressor response in both anesthetized and freely-moving mice. In addition, activation of CeM^GABA axonal terminals projecting to the nucleus tractus solitarius (NTS) significantly reduces blood pressure. These CeM^GABA neurons form synaptic connections with NTS neurons, allowing for the modulation of cardiovascular responses by influencing the caudal or rostral ventrolateral medulla. Furthermore, CeM^GABA neurons targeting the NTS receive dense inputs from the CeL. Consequently, stimulation of CeM^GABA neurons elicits hypotension through the CeM-NTS circuit, offering deeper insights into the cardiovascular responses associated with emotions and behaviors.
Animals ; GABAergic Neurons/physiology* ; Male ; Central Amygdaloid Nucleus/physiopathology* ; Hypotension/physiopathology* ; Mice ; Blood Pressure/physiology* ; Mice, Inbred C57BL ; Solitary Nucleus/physiology* ; Photic Stimulation ; Neural Pathways/physiology*

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 (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT 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 NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

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 ; Baroreflex ; physiology ; Blood Pressure ; drug effects ; Hypertension ; metabolism ; Hypoxia ; chemically induced ; Kidney ; drug effects ; metabolism ; Male ; Nitric Oxide Synthase Type I ; drug effects ; metabolism ; Rats, Sprague-Dawley ; Solitary Nucleus ; metabolism

The autonomic nervous system (ANS) integrates the function of the internal organs for the homeostasis against various external environmental changes. The efferent components of the ANS are regulated by sensory signals arising from the viscera as well as non-visceral organs. The central neural networks that integrate these sensory signals and modify visceral motor output are complex, and synaptic reflexes formed in the brainstem and spinal cord integrate behavioral responses and visceral responses through the central neural networks. A detailed understanding of the neural network presented above may explain the role of the vestibular system on the homeostasis more extensively.
Autonomic Nervous System ; Brain Stem ; Homeostasis ; Physiology ; Reflex ; Solitary Nucleus ; Spinal Cord ; Spinal Cord Lateral Horn ; Viscera

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 ; Afferent Pathways/physiology ; Animals ; Injections/veterinary ; Ligands ; Male ; Proto-Oncogene Proteins c-fos/*metabolism ; Quaternary Ammonium Compounds/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled/*metabolism ; Solitary Nucleus/*physiology ; Vagus Nerve/*drug effects/*physiology

The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M1 receptor antagonist, i.e., pirenzepine (PRZ), the M2 receptor antagonist, i.e., methoctramine (MTR) or the N1 receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H1 receptor antagonist, i.e., chlorpheniramine (CHL) or the H2 receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P < 0.05), shifted the middle part of ISP-Gain relationship curve upwards (P < 0.05), and increased reflex parameters such as the MAP range and maximum gain (P < 0.05), but decreased parameters such as saturation pressure and intracarotid sinus pressure at maximum gain (P < 0.05). The catabatic effects of pretreatment with MTR into the NTS on CSR resetting induced by i.c.v. HA were more obvious than those with PRZ (P < 0.05), but pretreatment of HEX with given dose into the NTS had no effects on CSR resetting induced by i.c.v. HA (P > 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M1 and M2 receptors mediation, especially the M2 receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H1 and H2 receptors mediation, especially the H1 receptors displaying effects.
Animals ; Baroreflex ; Carotid Sinus ; physiology ; Chlorpheniramine ; pharmacology ; Cholinergic Antagonists ; pharmacology ; Cimetidine ; pharmacology ; Histamine ; pharmacology ; Pressoreceptors ; physiology ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus ; physiology

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

OBJECTIVETo investigate the central mechanism of hypoglycemic effect induced by ear acupuncture.

METHODSExtracellular single-unit recordings were carried out in nucleus tractus solitarius (NTS) of rats after infusion of glucose, insulin via jugular venous and electroacupuncture at auricular concha, observing responses of glucose-sensitive neurons and insulin-sensitive neurons in NTS to electroacupuncture stimulation at auricular concha.

RESULTSThere existed glucose-sensitive neurons and insulin-sensitive neurons in NTS. Among glucose-sensitive neurons, inhibitory ones accounted for 37.3%, and excitable ones accounted for 10.9%. Among the insulin-sensitive neurons, excitable ones accounted for 33.3%, and inhibitory ones accounted for 4.9%. When electroacupuncture was given at auricular concha, 49.3% (34/69) of total neurons recorded in NTS showed increase in firing rate, while 4.3% (3/69) showed decrease in firing rate. Among the 34 exciting-responsive neurons, there were 18 neurons responding to glucose infusion with a discharge decreased in frequency, and there were 8 neurons responding to insulin infusion with a discharge increased in firing rate.

CONCLUSIONAcupuncture stimulation at auricular concha can irritate the neurons in NTS, which show largely inhibitory and excitable response to glucose and insulin infusion, respectively. The hypoglycemic effect induced by auricular acupuncture possibly results from regulating these neurons' firing activities.

Acupuncture, Ear ; Animals ; Electroacupuncture ; Glucose ; pharmacology ; Insulin ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus ; drug effects ; physiology

OBJECTIVETo probe into the bidirectional regulation of acupuncture in the rat with motility abnormality of the stomach and the nerve mechanism.

METHODSAdopting electrophysiological methods, the extracellular discharge signals of neuronic action in NTS were recorded with glass microelectrodes. The effects of acupuncture at "Zusanli" (ST 36), "Neiguan" (PC 6), "Zhongwan" (CV 12), "Qihai" (CV 6) on discharges of NTS neurons and intra-gastric pressure were observed in the rat at normal physiological state, and increase or reduction of gastric motility.

RESULTSAcupuncture at "Zusanli" (ST 36), "Neiguan" (PC 6) could significantly promote gastric motility of the rat at normal status, increase or reduction of gastric motion, while acupuncture at "Zhongwan" (CV 12), "Qihai" (CV 6) could significantly inhibit gastric motion. And acupuncture at all the above acupoints could activate discharges of NTS neurons.

CONCLUSIONThe bidirectional regulation effect of an acupoint does not certainly indicate that the same point has bidirectional regulation effect on an internal organs at different pathological states, while this may show synthetic action of different points which is a good regulation towards normal states and homeostasis.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Gastrointestinal Motility ; Male ; Rats ; Rats, Sprague-Dawley ; Solitary Nucleus ; physiology ; Stomach Diseases ; physiopathology ; therapy