Neurons In Medulla Oblongata Research Articles

Hepatic glycogenolysis and hypometabolism induced by chemogenetic stimulation of C1 neurons.

The precise regulation of blood glucose levels is indispensable for maintaining physiological functions. C1 neurons determine the outflow of the autonomic nervous and endocrine systems to maintain blood glucose levels in the body. In contrast, activation of C1 neurons induces a decrease in activity, suggesting that hypoactivity also participates in maintaining blood glucose levels. To examine this, we evaluated both glycogenolysis and hypometabolism induced by the selective activation of C1 neurons. We used DbhCre/0 mice expressing receptors for chemogenetic tools in C1 neurons, owing to microinjection of the viral vector. C1 neurons were activated by intraperitoneal injection of clozapine N-oxide (CNO). The chemogenetic activation of C1 neurons significantly decreased body temperature, oxygen consumption, and carbon dioxide production. On the other hand, the blood glucose level was increased by the activation of C1 neurons 2 h after CNO administration, even in the fasting state. In this situation, an increase in glucagon and corticosterone levels was observed, while hepatic glycogen content decreased significantly. Plasma insulin level was not changed by the activation of C1 neurons despite the blood glucose level increased. Furthermore, adrenal sympathetic nerve activity was significantly increased by the activation of C1 neurons, and plasma catecholamine levels increased significantly. In conclusion, the selective activation of C1 neurons using chemogenetic tools induced an increase in blood glucose level, probably because of hepatic glycogenolysis and hypometabolism. KEY POINTS: Chemogenetic activation of C1 neurons in medulla oblongata decreased body temperature. Oxygen consumption and carbon dioxide production were decreased by chemogenetic activation of C1 neurons in medulla oblongata. Blood glucose level was increased by chemogenetic activation of C1 neurons in medulla oblongata. Chemogenetic activation of C1 neurons in medulla oblongata increased glucagon, corticosterone, and catecholamine levels in plasma. Increase in blood glucose level by activation of C1 neurons occurred due to combined effect of hepatic glycogenolysis and hypometabolism. Abstract figure legend We investigated the effects of selectively activating C1 neurons using chemogenetic tools on blood glucose levels. The activation of C1 neurons resulted in an increase in blood glucose levels. This increase is due to the activation of hepatic glycogenolysis through the release of humoral factors, including adrenaline, glucagon, and corticosterone. Additionally, the decrease in energy expenditure, as evidenced by a reduction in body temperature, oxygen consumption, and carbon dioxide production, suggests that activation of C1 neurons may induce hypometabolism, which could also contribute to an increase in blood glucose levels. These responses indicate that C1 neurons may serve as a switch for energy conservation to maintain blood glucose levels, presumably by being activated in a stressful situation. This article is protected by copyright. All rights reserved.

Repeated activation of C1 neurons in medulla oblongata decreases anti-inflammatory effect via the hypofunction of the adrenal gland adrenergic response

The immune system is known to be controlled by the autonomic nervous system including sympathetic and parasympathetic (vagus) nerves. C1 neurons in the medulla oblongata, which participate in the control of the autonomic nervous system, are responders to stressors and regulate the immune system. Short-term activation of C1 neurons suppresses inflammation, while the effect of a long-term activation of these neurons on the inflammatory reflex is unclear. We, herein, demonstrate that the coactivation of both the splenic sympathetic nerves and the adrenal gland adrenergic response are indispensable for the prognosis of acute lung injury. The chemogenetic activation of C1 neurons increased plasma catecholamine including adrenaline and noradrenaline levels. The deletion of catecholaminergic cells using local injections of viral vector in the adrenal gland abolished the protective effect against acute lung injury when the C1 neurons were stimulated by either chemogenetic or optogenetic tools. Furthermore, repeated activation of C1 neurons using chemogenetic tool inhibited the adrenal response without affecting the plasma noradrenaline levels, eliminated the protective effect against acute lung injury. This was rescued by the isoprenaline administration. We concluded that the maintenance of an adrenergic response via C1 neurons in the adrenal gland is a prerequisite for the delivery of an effective anti-inflammatory response.

Galvanic vestibular stimulation-induced activation of C1 neurons in medulla oblongata protects against acute lung injury.

Autonomic nerves, including the sympathetic and parasympathetic nerves, control the immune system along with their physiological functions. On the peripheral side, the interaction between the splenic sympathetic nerves and immune cells is important for the anti-inflammatory effects. However, the central mechanism underlying these anti-inflammatory effects remains unclear. C1 neurons respond to stressors and subsequently determine the outflow of the autonomic nervous system. We have previously shown that C1 neurons protect against acute kidney injury and found a signaling connection between peripheral vestibular organs and C1 neurons. Thus, we hypothesized that hypergravity load or galvanic vestibular stimulation (GVS) might protect against acute lung injury. We showed that C1 neurons are histologically and functionally activated by stimulating the peripheral vestibular organs. Protection against acute lung injury that was induced by a 2 G load disappeared due to vestibular lesions or the deletion of C1 neurons. This GVS-induced protective effect was also eliminated by the deletion of the C1 neurons. Furthermore, GVS increased splenic sympathetic nerve activity in conscious mice, and splenic sympathetic denervation abolished the GVS-induced protection against acute lung injury. Therefore, the activated pathway between C1 neurons and splenic sympathetic nerves is indispensable for GVS-induced protection against acute lung injury.

A rare case of possible vacuolar degeneration of leprosy in brain with segmental necrotizing granulomatous neuritis and horner's syndrome

Leprosy has a predilection for peripheral nerves, but rarely does it involve the central nervous system (CNS). There is a single study of CNS involvement in leprosy showing vacuolar changes of motor neurons in medulla oblongata and spinal cord in autopsy findings. Besides this, there has been only one case report providing direct histopathological and molecular evidence of CNS involvement by leprosy in a living patient. Segmental necrotizing granulomatous neuritis (SNGN) is a rare condition affecting the peripheral nerves in leprosy usually seen as a complication of tuberculoid (TT) and borderline tuberculoid (BT) leprosy. We report the case of a 23-year-old male patient, a case of Hansen's disease (BT) who developed CNS involvement in the form of partial Horner's syndrome (right) and SNGN while on treatment. Magnetic resonance imaging of the brain revealed T2 hyperintense lesion on the dorsal aspect of left pontomedullary junction, suggestive of vacuolar degeneration of leprosy. Histopathology of greater auricular nerve (right) revealed SNGN.

Neuronal activity of the medulla oblongata revealed by manganese-enhanced magnetic resonance imaging in a rat model of gastroesophageal reflux-related cough.

We investigated neuronal activity of the medulla oblongata during gastroesophageal reflux-related cough (GERC). A rat model of GERC was generated by perfusing HCl into lower esophagus and inducing cough with citric acid. The HCl group rat was received HCl perfusion without citric acid-induced cough. The saline control rat was perfused with saline instead and cough was induced. Citric acid-induced cough rat was only induced by citric acid. Blank group rats were fed normally. Fos expressions were observed in medulla oblongata nuclei using immunohistochemistry. Manganese-enhanced magnetic resonance imaging (MEMRI) was performed to detect the Mn(2+) signal following intraperitoneal injection of MnCl(2). HCl perfusion and citric acid-induced cough caused Fos expressions in the nucleus of solitary tract (nTS), dorsal motor nucleus of the vagus (DMV), paratrigeminal nucleus (Pa5), and intermediate reticular nucleus (IRt), which was higher than HCl group, saline control group, citric acid-induced cough group, and blank group. A high Mn(2+) signal was also observed in most of these nuclei in model rats, compared with blank group animals. The Mn(2+) signal was also higher in the HCl, saline and citric acid-induced cough group animals, compared with blank group animals. The study showed medulla oblongata neurons were excited in a HCl perfusion and citric acid-induced cough rat model, and nTS, DMV, Pa5 and IRt neurons maybe involved in the cough process and signal integrate.

Mitochondrial HSP60 Protein in Rat Medulla Oblongata Cells

HSP60 is a member of the heat shock protein (HSP) group and is located predominantly in cell mitochondria. Dysfunction and insufficient synthesis of HSP60 in the nervous system leads to neurodegeneration. The aim of the present work was to conduct immunohistochemical determination of the location of HSP60 protein in neurons and gliocytes in the medulla oblongata in rats. Studies were performed on mature male Wistar rats weighing 200–250 g (n = 7). The results provided evidence that HSP60 has a discrete localization in cytoplasmic structures in neurons and gliocytes. In large neurons, local accumulation of HSP60 allows fine structures to be detected, probably mitochondria. An important observation is that of the absence of any cytosolic reaction in medulla oblongata neurons and gliocytes. This provides grounds for using the reaction for HSP60 in complex studies of apoptosis in nerve cells, as this is associated with an accumulation of HSP60 and displacement of immunopositive product to the plasmalemma.

Vagotomy decreases the neuronal activities of medulla oblongata and alleviates neurogenic inflammation of airways induced by repeated intra-esophageal instillation of HCl in guinea pigs.

Neuronal activity in the medulla oblongata and neurogenic inflammation of airways were investigated in a guinea pig model induced by repeated intra-esophageal instillation of hydrochloric acid (HCl) after vagotomy. Unilateral vagotomy was performed in the vagotomy group, while a sham-operation was performed in the sham group. Operation was not conducted in sham control group. Airway inflammation was observed with hematoxylin and eosin (HE) staining. C-fos protein was measured by immunohistochemistry (IHC) and Western blot (WB). Substance P was examined by IHC and enzyme-linked immuno sorbent assay (ELISA). Airway microvascular permeability was detected by evans blue dye (EBD) fluorescence. Inflammation of airway was observed in the trachea and bronchi after chronic HCl perfusion into the lower esophagus, and was alleviated after unilateral vagotomy. C-fos expression in the medulla oblongata was lower in the vagotomy group compared to the sham control and sham groups. Substance P-like immunoreactivity (SP-li), concentration and microvascular leakage in airway were lower in the vagotomy group than that in the other groups. Our results suggest that vagotomy improved neurogenic inflammation of airways and decreased neuronal activities, the afferent nerves and neurons in medulla oblongata may be involved in neurogenic inflammation of airways mediated by esophageal-bronchial reflex.

NO-ergic Control of Blood Circulation in the Medulla Oblongata of Rats with Experimental Hemiparkinsonism under Prolonged Exposure to Continuous Light

The study was conducted on rats with unilateral damage to dopaminergic (DA) neurons in substantia nigra of the midbrain (experimental hemiparkinsonism). Degeneration of dopaminergic (DA) neurons was accompanied by hyperactivity of those neurons that remained intact and responded to apomorphine (Apo) test by rotational movements. Depending on the number of rotations, three groups of animals were defined. In the medulla oblongata of rats with unilateral damage to dopaminergic (DA) neurons, a significant increase in the activity of inducible NO-synthase (iNOS) was observed, while the activity of constitutive NO-synthase (cNOS) tended to decrease compared with that in control rats. An activation of neuronal NOsynthase (nNOS) in those rats by injections of L-arginine in the medullary nuclei was accompanied by weakening the hemodynamic effects compared to those in control rats. An exposure of animals to all-night light for three weeks was accompanied by increasing the number of damaged DA-ergic neurons in substantia nigra. At that, a significant decrease in cNOS activity in the medulla oblongata was observed, leading to the inhibition of de novo synthesis of nitric oxide (NO). The reduction of NO synthesis in the medulla oblongata neurons of rats with experimental hemiparkinsonism following their exposure to continuous light was also evidenced by the reduction of the amount of nitrite (NO2-) anion.

NO-ERGIC CONTROL OF BLOOD CIRCULATION IN THE MEDULLA OBLONGATA OF RATS WITH EXPERIMENTAL HEMIPARKINSONIZM UNDER EXPOSURE TO CONTINUOUS LIGHT.

The study was conducted on rats with unilateral damage to dopaminergic (DA) neurons in substantia nigra of the midbrain (experimental hemiparkinsonism). Degeneration of dopaminergic (DA) neurons was accompanied by hyperactivity of those neurons that remained intact and responded to apomorphine (Apo) test by rotational movements. Depending on the number of rotations, three groups of animals were defined. In the medulla oblongata of rats with unilateral damage to dopaminergic (DA) neurons, a significant increase in the activity of inducible NO-synthase (iNOS) was observed, while the activity of constitutive NO-synthase (cNOS) tended to decrease compared with that in control rats. An activation of neuronal NO-synthase (nNOS) in those rats by injections of L-arginine in the medullary nuclei was accompanied by weakening of the hemodynamic effects compared to those in control rats. An exposure of animals to continuous light for three weeks was accompanied by increasing the number of damaged DA-ergic neurons in substantia nigra. At that, a significant decrease in cNOS activity in the medulla oblongata was observed, leading to the inhibition of de novo synthesis of nitric oxide (NO). The reduction of NO synthesis in the medulla oblongata neurons of rats with experimental hemiparkinsonism following their exposure to continuous light was also evidenced by the reduction.

Three-dimensional organization of the cytoplasmic neuroglobin-immunopositive structures in the rat medulla oblongata neurons

Neuroglobin is an iron-containing protein, most abundant in the vertebrate nervous system. Since neuroglobin is able to bind oxygen reversibly owing to the heme prosthetic group, it was believed that its function is an intercellular transport of oxygen in the nervous system and accumulation of oxygen for energy supply of cells in hypoxic conditions. In this work, a three-dimensional reconstruction of the neuroglobin distribution in large neurons of the rat medulla oblongata was carried out by means of immunocytochemistry and confocal laser microscopy. Positive neuroglobin immunocytochemical reaction was observed mainly in the perinuclear areas of large nerve cells exhibiting a discrete staining of the cytoplasm. Examination under the microscope at a high magnification revealed some neuroglobin-immunopositive granules, ring-like objects 1–2 μm in diameter, as well as linear and branched structures in neuronal cytoplasm and, occasionally, in the proximal segments of neuronal processes. Three-dimensional reconstruction of the neuroglobin-immunopositive structures showed that they mainly have the form of continuous lines and curves interlaced in some sites, about 1.0–1.5 μm thick, forming a complex network in the cytoplasm. The neuroglobin-immunopositive complexes found for the first time in neuronal cytoplasm are not identical to any known cytoplasmic compartments of nerve cells, but the diameter of their elements, as well as the shape and location suggest a possible link of neuroglobin with a mitochondrial network.

Effect of transient receptor potential vanilloid-1 on cough hypersensitivity induced by particulate matter 2.5

AimsThe mechanism of cough hypersensitivity induced by particulate matter 2.5 (PM2.5) remains elusive. The current study was designed to explore the effect of transient receptor potential vanilloid-1 (TRPV1) on cough hypersensitivity in airway and central nervous system. Main methodsThe PM2.5-induced chronic cough model of guinea pig was established by exposure to different doses of PM2.5 for three weeks. After exposure, the animals were microinjected with TRPV1 agonist capsaicine, antagonist capsazepine in the dorsal vagal complex respectively. Cough sensitivity was measured by determining the provocative concentration of citric acid inducing 5 or more coughs (C5). Airway inflammation was detected by hematoxylin eosin (HE) staining and Evans blue fluorescence, and substance P (SP) and TRPV1 expressions in airway were observed by immunohistochemical staining. TRPV1 expressions in the dorsal vagal complex were observed by immunofluorescence. Retrograde tracing by pseudorabies virus-Bartha (PRV-Bartha) was conducted to confirm the regulatory pathway between airway and central nervous system. Key findingsPM2.5 induced TRPV1 expressions in both of airway and dorsal vagal complex and airway neurogenic inflammation. Airway vascular permeability increased after being exposed to PM2.5. The expressions of SP in the airway and airway inflammation was increased after microinjecting TRPV1 agonist, and decreased after microinjecting TRPV1 antagonist. PRV infected neurons in medulla oblongata mainly located in the dorsal vagal complex. SignificanceThese findings show that TRPV1 in the dorsal vagal complex could promote airway neurogenic inflammation and cough reflex sensitivity through neural pathways of vagal complex-airways, which indicate the therapeutic potential of specific inhibition of TRPV1 for chronic cough induced by PM2.5.

Brainstem hypoxia contributes to the development of hypertension in the spontaneously hypertensive rat.

Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O2 sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal PO2 in the spontaneously hypertensive rat was found to be ≈15 mm Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower PO2 of brainstem parenchyma may be associated with higher levels of ambient ATP and l-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure.

Protein kinase A mediates adenosine A2a receptor modulation of neurotransmitter release via synapsin I phosphorylation in cultured cells from medulla oblongata

Synaptic transmission is an essential process for neuron physiology. Such process is enabled in part due to modulation of neurotransmitter release. Adenosine is a synaptic modulator of neurotransmitter release in the Central Nervous System, including neurons of medulla oblongata, where several nuclei are involved with neurovegetative reflexes. Adenosine modulates different neurotransmitter systems in medulla oblongata, specially glutamate and noradrenaline in the nucleus tractussolitarii, which are involved in hypotensive responses. However, the intracellular mechanisms involved in this modulation remain unknown. The adenosine A2a receptor modulates neurotransmitter release by activating two cAMP protein effectors, the protein kinase A and the exchange protein activated by cAMP. Therefore, an in vitro approach (cultured cells) was carried out to evaluate modulation of neurotransmission by adenosine A2a receptor and the signaling intracellular pathway involved. Results show that the adenosine A2a receptor agonist, CGS 21680, increases neurotransmitter release, in particular, glutamate and noradrenaline and such response is mediated by protein kinase A activation, which in turn increased synapsin I phosphorylation. This suggests a mechanism of A2aR modulation of neurotransmitter release in cultured cells from medulla oblongata of Wistar rats and suggest that protein kinase A mediates this modulation of neurotransmitter release via synapsin I phosphorylation.

Modulation of Na+, K+-ATPase Activity in the Medulla Oblongata Neurons Affects Hemodynamics in Spontaneously Hypertensive Rats

Modulation of Na+, K+-ATPase Activity in the Medulla Oblongata Neurons Affects Hemodynamics in Spontaneously Hypertensive Rats

Effects of Electrical Stimulation of the Hunger Center in the Lateral Hypothalamus and Food Reinforcement on Impulse Activity of the Stomach in Rabbits under Conditions of Hunger and Satiation

Stimulation of the lateral hypothalamus in preliminary fed animals in the presence of the food is associated with successful food-procuring behavior, accompanied by regular generation of high-amplitude slow electrical waves by muscles of the lesser curvature, body, and antrum of the stomach, which was reflected in the structure of temporal organization of slow electrical activity in the form of unimodal distribution of slow wave periods typical of satiation state. Despite increased level of food motivation caused by stimulation of the lateral hypothalamus, the additional food intake completely abolished the inhibitory effects of hunger motivation excitement on slow electrical muscle activity in the lesser curvature, body, and antrum of the stomach of satiated rabbits. Changes in slow electrical activity of the stomach muscles in rabbits deprived of food over 24 h and offered food and associated food-procuring behavior during electrical stimulation of the lateral hypothalamus have a two-phase pattern. Despite food intake during phase I of electrical stimulation, the downstream inhibitory effect of hunger motivation excitement on myogenic pacemaker of the lesser curvature of stomach abolishes the stimulating effect of food reinforcement on slow electrical muscle activity in the lesser curvature, body, and antrum of the stomach. During phase II of electrical stimulation, the food reinforcement decreases inhibitory effect of hunger motivation excitement on myogenic pacemaker of the lesser curvature that paces maximal rhythm of slow electrical waves for muscles activity in the lesser curvature, body, and antrum of the stomach, which is reflected by unimodal distribution of slow electrical wave periods. Our results indicated that the structure of temporal organization of slow electrical activity of the stomach muscles reflects convergent interactions of food motivation and reinforcement excitations on the dorsal vagal complex neurons in medulla oblongata.

NAADP-mediated channel ‘chatter’ in neurons of the rat medulla oblongata

NAADP (nicotinic acid-adenine dinucleotide phosphate) is a potent Ca(2+)-mobilizing messenger that stimulates Ca(2+) release in a variety of cells. NAADP-sensitive Ca(2+) channels are thought to reside on acidic Ca(2+) stores and to be functionally coupled to IP(3) (inositol 1,4,5-trisphosphate) and/or ryanodine receptors located on the endoplasmic reticulum. Whether NAADP-sensitive Ca(2+) channels 'chatter' to other channels, however, is not clear. In the present study, we have used a cell-permeant NAADP analogue to probe NAADP-mediated responses in rat medulla oblongata neurons. NAADP-AM (NAADP-acetoxymethyl ester) evoked global cytosolic Ca(2+) signals in isolated neurons that were reduced in amplitude by removal of external Ca(2+), abolished by disruption of acidic compartments and substantially inhibited by blockade of ryanodine receptors. In rat medullary slices, NAADP-AM depolarized neurons from the nucleus ambiguus in the presence of intracellular EGTA, but not of the faster Ca(2+) chelator BAPTA [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid]. Depolarization was also dependent upon extracellular Ca(2+), acidic stores and ryanodine receptors. In voltage-clamp mode, NAADP-AM induced an inward current with a reversal potential of approx. 0 mV. The results of the present study reveal the presence of acidic NAADP-sensitive Ca(2+) stores in medulla neurons, the mobilization of which results not only in global Ca(2+) signals but also in local signals that activate non-selective cation channels on the cell surface resulting in depolarization. Thus NAADP is capable of co-ordinating channels both within the cell interior and at the cell membrane representing a novel mechanism for excitation of central neurons.

Adenosine A 2A receptors are expressed by GABAergic neurons of medulla oblongata in developing rat

During early development, adenosine contributes to the occurrence of respiratory depression and recurrent apneas. Recent physiological studies indicate that GABAergic mechanisms may be involved in this inhibitory action of adenosine, via their A 2A receptors. In the present study, in situ hybridization with ribonucleotide probes for A 2A receptor (A 2AR) mRNA was combined with the immunolabeling technique for parvalbumin and transneuronal retrograde tracing method using green fluorescent protein expressing pseudorabies virus (GFP-PRV) to (1) characterize age-dependent changes in the expression of adenosine A 2ARs mRNA in brain stem regions where GABAergic neurons are located; (2) determine whether GABA-containing neurons express A 2AR mRNA traits, and (3) identify whether bulbospinal GABAergic neurons projecting to phrenic nuclei contain A 2AR mRNA. Results revealed expression of A 2A receptors in regions of medulla oblongata containing GABAergic neurons, namely in the ventral aspect of the medulla, within the Bötzinger region and caudal to it, the gigantocellular reticular nucleus, midline neurons and the caudal ventrolateral medulla oblongata. Furthermore, a subpopulation of identified GABAergic neurons, projecting to the phrenic motor nuclei, possess A 2AR mRNA. It is concluded that adenosine A 2ARs expressed by GABAergic neurons are likely to play a role in mediating adenosine-induced respiratory depression.

Vagal Stimulation Modifies Parameters of Heterochromatin in the Nuclei of Vagosolitary Complex Neurons of Medulla Oblongata in Rats

New data were obtained on modification of heterochromatin parameters in the nuclei of medulla oblongata neurons in Wistar rats after stimulation of the vagus nerve: decrease in the area of heterochromatin regions and redistribution of chromocenters within the neuronal nuclear system. It was concluded that realization of the viscero-visceral reflex is associated with rearrangement of chromatin in neurons involved in transmission of the corresponding information.

Late vagal inhibition in neurons of the ventrolateral medulla oblongata in the rat

Stimulation of cervical vagal afferents elicits long-lasting inhibitory effects in a variety of neuronal populations, although little is known concerning the cellular mechanisms that are involved in these effects. In the present study, the electrophysiological characteristics of responses elicited by cumulative activation of vagal afferents were examined in neurons of the rostral ventrolateral medulla oblongata, which play an important role in the coordination of cardiovascular and other visceral activities. The study has focused on the late-onset, slow inhibitory component of vagal responses, which is likely to affect the temporal modulation of postsynaptic effects. Vagal stimulation elicited four distinct response patterns in intracellularly penetrated neurons ( n=78): excitation, inhibition, excitation–inhibition and inhibition–inhibition. The late inhibitory component was encountered in 43 (55%) of the cells, including five putative medullospinal neurons. It was due to a postsynaptic hyperpolarization which reversed at potentials more negative than −83 mV. The voltage dependency, as well as the average onset latency (93±3.0 ms), duration (270±16.5 ms) and amplitude (1.3±0.2 mV as measured at resting membrane potentials), of late inhibition were clearly different from those of the short-latency inhibitory response. The differences in the voltage dependency and time-course of the short-latency responses and the late inhibition indicate that they are mediated by different central relays. In the majority of neurons, late inhibition could be elicited by stimulating only myelinated vagal afferents. The magnitude of the response was, however, significantly enhanced in 63% of the examined cells when the intensity of stimulation was raised to recruit further myelinated and non-myelinated fibres. This indicates that late vagal inhibition is often elicited by a cumulative activation of convergent afferent inputs. The intracellularly labelled vagally responsive neurons were present at all rostrocaudal levels of the rostral ventrolateral medulla, with an accumulation in the region of the lateral paragigantocellular nucleus. Neurons that exhibited late vagal inhibition were dominant in the juxtafacial region of this nucleus. Due to its slow time-course, late vagal inhibition may contribute to a tonic modulation of the activity of neurons in the rostral ventrolateral medulla oblongata. It is proposed that late vagal inhibition plays an important role in the temporal integration of sensory inputs in neurons of the rostral ventrolateral medulla oblongata. The time-course and strength of this modulatory effect are related to the level of activity in those visceral sensory inputs that converge onto the inhibitory interneurons that mediate late inhibition to rostral ventrolateral medulla oblongata neurons.

Vagal modulation of responses elicited by stimulation of the aortic depressor nerve in neurons of the rostral ventrolateral medulla oblongata in the rat

Stimulation of cervical vagal afferents inhibits central sympathetic outflows in part by inhibiting the ongoing activity of putative baroreceptive neurons in the rostral ventrolateral medulla oblongata. The aim of the present study was to examine the electrophysiological characteristics of vagal responses and their interactions with responses elicited by stimulation of the aortic nerve in neurons there. The study focused on the role of the long-lasting, late-onset vagal inhibition, which is likely to play an important role in the tonic inhibitory effects of vagal afferent stimulation. In vivo intracellular recordings were obtained from 33 neurons that received convergent inputs from aortic and vagal afferents. Sixty-four percent of these neurons exhibited a late inhibition following electrical stimulation of myelinated vagal afferents (mean onset latency of 100±5 ms). The average duration of late inhibition (294±19 ms) exceeded the duration of the cardiac cycle. As a consequence of this, sustained vagal stimulation diminished the effect of rhythmic baroreceptor inputs in neurons that exhibited late vagal inhibition. Simultaneous activation of aortic and vagal afferents significantly increased the magnitude of late inhibition, even in those neurons where stimulation of the aortic nerve alone did not elicit a response ( n=15). This suggested that the convergence between vagal and aortic afferent inputs occurred in inhibitory interneurons antecedent to the recorded rostral ventrolateral medulla oblongata neurons. Focal stimulation of the caudal part of the nucleus of the solitary tract also elicited a late-onset inhibition in 73% of the neurons that responded to stimulation of the aortic nerve. This inhibition appeared to be similar to the late vagal inhibition, except for its shorter average onset latency (64±7 ms). Based on this observation, it is proposed that inhibitory interneurons that mediate late inhibition to rostral ventrolateral medulla oblongata neurons may lie within the caudal part of the nucleus of the solitary tract. The present study established that activation of myelinated vagal afferents exerts a complex modulation over the ongoing and evoked activity of neurons that respond to stimulation of the aortic nerve. The complex interaction that occurs between aortic and vagal inputs in neurons of the rostral ventrolateral medulla may be implicated in long-term modulation of sympathetic outflows in response to changes in the activation of visceral receptors supplied by vagus afferents. The modulation elicited by late vagal inhibition may help to adjust cardiovascular outflows according to requirements set by the thoraco-abdominal visceral environment.