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 (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb 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 NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb 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 NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*

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*

Neuronal activities of taste-responsive cells in the nucleus of the solitary tract (NST) are affected by various physiological factors, such as blood glucose level or sodium imbalance. These phenomena suggest that NST taste neurons are under the influence of neural substrates that regulate nutritional homeostasis. In this study, we reviewed a series of in vivo electrophysiological investigations that demonstrate that forebrain nuclei, such as the lateral hypothalamus or central nucleus of the amygdala, send descending projections and modulate neuronal activity of gustatory neurons in the NST. These centrifugal modulations may mediate plasticity of taste response in the NST under different physiological conditions.
Amygdala ; Blood Glucose ; Homeostasis ; Hypothalamus ; Neurons* ; Plastics ; Prosencephalon ; Sodium ; Solitary Nucleus*

Taste receptors of the anterior tongue are innervated by the chorda tympani (CT) branch of the facial (VIIth) nerve. The CT nerve transmits information on taste to the ipsilateral nucleus of the solitary tract (NST), which is the first taste central nucleus in the medulla. Taste information is known to be transferred ipsilaterally along the taste pathway in the central nervous system. Some patients with unilateral CT damage often retain their ability to sense taste. This phenomenon is not explained by the unilateral taste pathway. We examined whether neurons in the NST receive information on taste from the contralateral side of the tongue by measuring c-Fos-like Immunoreactivity (cFLI) following taste stimulation of the contralateral side of the tongue in the anesthetized rats. We used four basic taste stimuli, 1.0 M sucrose, 0.3 M NaCl, 0.01 M citric acid, 0.03 M QHCl, and distilled water. Stimulation of one side of the tongue with taste stimuli induced cFLI in the NST bilaterally. The mean number of cFLI ranged from 23.28 +/- 2.46 by contralateral QHCl to 30.28 +/- 2.26 by ipsilateral NaCl stimulation. The difference between the number of cFLI in the ipsilaterl and contralateral NST was not significant. The result of the current study suggests that neurons in the NST receive information on taste not only from the ipsilateral but also the contralateral side of the tongue.
Animals ; Central Nervous System ; Citric Acid ; Humans ; Neurons ; Rats ; Solitary Nucleus ; Sucrose ; Tongue ; Water

BACKGROUND AND OBJECTIVES: Central role of the vestibular system on control of blood pressure and interrelationships between the vestibular nucleus and solitary nucleus during acute hypotension were investigated in bilateral labyrinthectomized (BLX) or sinoaortic denervated (SAD) rats. Changes of electrical activity in the medial vestibular nucleus (MVN), solitary tract nucleus (STN), and rostral ventrolateral medullary nucleus (RVLM) were investigated in rats in while acute hypotension was induced by sodium nitroprusside (SNP). RESULTS: Evoked potential in MVN neuron caused by electrical stimulation of the peripheral vestibular system was composed of 3 waves with latencies of 0.48+/-.10 ms, 1.04+/-.09 ms and 1.98+/-.19 ms. Electrical stimulation to MVN or RVLM increased blood pressure. MVN at the induction of acute hypotension showed excitation in 61% of type I neurons and inhibition in 68% of type II neurons. In STN, acute hypotension produced excitation in 62.1% of neurons recorded in intact labyrinthine animals, inhibition in 72.3% of neurons recorded in BL animals, and excitation in 60% of recorded neurons in SAD animals. In RVLM, acute hypotension produced excitation in 66.7% of neurons recorded in intact labyrinthine animals and inhibition in 64.9% of neurons recorded in BL animals. In spatial distribution of STN neurons responded to acute hypotension, excitatory responses were mainly recorded in rostral and ventral portion, and inhibitory responses were mainly recorded in caudal and lateral portion. In RVLM, excitatory responses were mainly recorded in rostral and dorsomedial portion, and inhibitory responses were mainly recorded in caudal and ventrolateral portion. CONCLUSION: These results suggest that afferent signals from the peripheral vestibular receptors are transmitted to STN through the vestibular nuclei and assist to the baroreceptors for controlling blood pressure following acute hypotension.
Animals ; Blood Pressure* ; Electric Stimulation ; Evoked Potentials ; Hypotension* ; Neurons ; Nitroprusside ; Pressoreceptors ; Rats* ; Solitary Nucleus ; Vestibular Nuclei

These experiments were performed to investigate the effect of saline, melatonin, stress, stressed-melatonin on serotonin immunoreactivity in rat brain stem. The animals were injected with melatonin (1 mg/kg, i.p.) after electric shocks for 15days. The results were as follows; 1. Serotonin immunoreactive neurons in brain stem (the number of staining neuron & the stain intensity in dorsal raphe nucleus of midbrain, the stain intensity in nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla oblongata) were decreased in melatonin treated group compared with all the other groups. 2. Serotonin immunoreactive neurons in brain stem (the number of staining neuron & the stain intensity in dorsal raphe nucleus of midbrain, the stain intensity in nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla oblongata) were significantly increased in stressed group compared with all the other groups. 3. Serotonin immunoreactive neurons in brain stem(the number of staining neuron & the stain intensity in dorsal raphe nucleus of midbrain, the stain intensity in nucleus tractus solitarius and dorsal raphe nucleus of vagus nerve in medulla oblongata) were significantly decreased in stressed-melatonin treated group compared with only stressed group but were significantly increased compared with melatonin treated group. These experiments indicate that serotonin immunoreactive neurons in dorsal raphe nucleus of midbrain were increased, due to the activation of stress, and decreased when the activating of stress is suppressed through melatonin treatment.
Animals ; Brain Stem* ; Brain* ; Melatonin* ; Mesencephalon ; Neurons ; Raphe Nuclei ; Rats* ; Serotonin ; Shock ; Solitary Nucleus ; Vagus Nerve

The purpose of the present study was to elucidate the possible involvement of the medial vestibular nucleus (MVN) and inferior vestibular nucleus (IVN) following acute hypotension in the vestibulo- autonomic reflex through vestibulosolitary or vestibuloventrolateral projections. Acute hypotension- induced cFos expression was assessed in combination with retrograde cholera toxin B subunit (CTb) tract tracing. After injection of CTb into the solitary region, CTb-labeled neurons were located prominently around the lateral borders of the caudal MVN and medial border of the IVN. The superior vestibular nucleus also had a scattered distribution of CTb-labeled neurons. After injection of CTb toxin into the unilateral VLM, the distributions of CTb-labeled neurons in the MVN and IVN were similar to that observed after injection into the solitary region, although there were fewer CTb-labeled neurons. In the caudal MVN, about 38% and 13% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. In the IVN, 14% and 7% of CTb-labeled neurons were double-labeled for cFos after injection of CTb into the solitary region and the VLM, respectively. Therefore, the present study suggests that acute arterial hypotension may result in activation of vestibulosolitary pathways that mediate behavioral and visceral reflexes, and vestibuloventrolateral medullary pathways that indirectly mediate vestibulosympathetic responses.
Animals ; Brain Stem* ; Brain* ; Cholera Toxin ; Hypotension* ; Neurons* ; Rats* ; Reflex ; Solitary Nucleus ; Vestibular Nuclei

Accumulating evidence demonstrates that the nucleus tractus solitarii (NTS) neurons serve as central respiratory chemoreceptors, but the underlying molecular mechanisms remain undefined. The present study investigated the expression of acid-sensitive ether-à-go-go-gene-like (Elk, Kv12) channels in the NTS of mice. Immunofluorescence staining was used to observe the distribution and cellular localization of the Kv12 channels in NTS neurons. Western blot and quantitative real-time PCR (qPCR) were used to evaluate protein and mRNA expression levels of Kv12 channels. The results showed that all of the three members (Kv12.1, Kv12.2, Kv12.3) of the Kv12 channel family were expressed in NTS neurons, and their expressions were co-localized with paired-like homeobox 2b gene (Phox2b) expression. The expression of Kv12.1 mRNA was the largest, whereas the expression of Kv12.3 was the least in the NTS. The results suggest Kv12 channels are expressed in Phox2b-expressing neurons in the NTS of mice, which provides molecular evidence for pH sensitivity in Phox2b-expressing NTS neurons.
Animals ; Mice ; Neurons ; Potassium Channels, Voltage-Gated ; Solitary Nucleus ; Transcription Factors/genetics*

BACKGROUND AND OBJECTIVES The temporal changes and the role of glutamate receptors in the recovery of vestibulogastrointestinal symptoms following unilateral labyrinthectomy (UL) were investigated in this study. Vestibulogastrointestinal symptoms were evaluated in terms of gastric emptying and intestinal transit. MATERIALS AND METHODS Expression of the c-Fos protein was observed in the solitary tract nucleus (STN) and rostral ventrolateral medullary nucleus (RVLM). These were measured at 0.5, 2, 6 and 24 h following UL in rats. RESULTS Gastric emptying and intestinal transit were significantly decreased for 6 h post UL and recovered to control levels within 24 h. Pretreatment of UL animals with MK-801 significantly increased the gastric emptying and intestinal transit. Bilateral labyrinthectomy significantly decreased the gastric emptying and intestinal transit compared to the intact labyrinthine animals but significantly increased when compared to UL animals. The expression of c-Fos protein was significantly increased in STN and RVLM compared to the control animals for 6 h post UL and recovered to control levels within 24 h. The expression was significantly decreased in animals that were pretreated with MK-801. CONCLUSION These results suggest that UL decreases the gastrointestinal motility, which recovers to control levels within 24 h post UL. Glutamate plays an important role in the recovery of vestibulogastrointestinal symptoms following UL.
Animals ; Dizocilpine Maleate ; Gastric Emptying ; Gastrointestinal Motility ; Glutamic Acid ; Receptors, Glutamate ; Solitary Nucleus

Salt signals in tongue are relayed to the nucleus of the solitary tract (NST). This signaling is very important to determine whether to swallow salt-related nutrition or not and suggests some implications in discrimination of salt concentration. Salt concentration-dependent electrical responses in the chorda tympani and the NST were well reported. But salt concentration-dependency and spatial distribution of c-Fos in the NST were not well established. In the present study, NaCl signaling in the NST was studied in urethane-anesthetized rats. The c-Fos immunoreactivity in the six different NST areas along the rostral-caudal axis and six subregions in each of bilateral NST were compared between applications of distilled water and different concentrations of NaCl to the tongue of experimental animals. From this study, salt stimulation with high concentration (1.0 M NaCl) induced significantly higher c-Fos expression in intermediate NST and dorsal-medial and dorsal-middle subregions of the NST compared to distilled water stimulation. The result represents the specific spatial distribution of salt taste perception in the NST.
Animals ; Axis, Cervical Vertebra ; Chorda Tympani Nerve ; Discrimination (Psychology) ; Rats ; Solitary Nucleus ; Taste Perception ; Tongue ; Water