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The Journal of Physiology Sep 19931. Neurons from a horizontal slice of adult rat brainstem were examined using intracellular recording techniques. Investigations were restricted to a region within the...
1. Neurons from a horizontal slice of adult rat brainstem were examined using intracellular recording techniques. Investigations were restricted to a region within the nucleus tractus solitarii, medial to the solitary tract and centred on the obex (mNTS). Previous work has shown this restricted area of the NTS to contain the greatest concentration of aortic afferent baroreceptor terminal fields. Electrical stimulation of the tract elicited short-latency excitatory postsynaptic potentials in all neurons. 2. mNTS neurons were spontaneously active with firing frequencies ranging between 1 and 10 Hz, at resting potentials of -65 to -45 mV. These neurons did not exhibit spontaneous bursting activity. 3. Depolarizing current injection immediately evoked a finite, high-frequency spike discharge which rapidly declined to a lower steady-state level (i.e. spike frequency adaptation, SFA). Increasing depolarizations produced a marked increase in the peak instantaneous frequency but a much smaller increase in the steady-state firing level. 4. Conditioning with a hyperpolarizing prepulse resulted in a prolonged delay of up to 600 ms before the first action potential (i.e. delayed excitation, DE) with an attendant decrease in peak discharge rates. DE was modulated by both the magnitude and duration of the prestimulus hyperpolarization, as well as the magnitude of the depolarizing stimulus. Tetrodotoxin (TTX) eliminated spike discharge but had little effect on the ramp-like membrane depolarization characteristic of DE. 5. We have developed a mathematical model for mNTS neurons to facilitate our understanding of the interplay between the underlying ionic currents. It consists of a comprehensive membrane model of the Hodgkin-Huxley type coupled with a fluid compartment model describing cytoplasmic [Ca2+]i homeostasis. 6. The model suggests that (a) SFA is caused by an increase in [Ca2+]i which activates the outward K+ current, IK,Ca, and (b) DE results from the competitive interaction between the injected depolarizing current and the hyperpolarization-activated transient outward K+ currents, IA and ID. 7. We conclude that our ionic current model is capable of providing biophysical explanations for a number of phenomena associated with brainstem neurons, either during spontaneous activity or in response to patterned injections of current. This model is a potentially useful adjunct for on-going research into the central mechanisms involved in the regulation of both blood pressure and ventilation.
Topics: Action Potentials; Animals; Calcium; Calcium-Transporting ATPases; Electric Stimulation; Electrophysiology; In Vitro Techniques; Ion Channels; Ion Exchange; Male; Membrane Potentials; Microelectrodes; Models, Neurological; Neurons; Neurons, Afferent; Potassium Channels; Rats; Rats, Sprague-Dawley; Sodium Channels; Solitary Nucleus
PubMed: 7505824
DOI: 10.1113/jphysiol.1993.sp019817 -
Molecular Pain 2018Background The mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle hyperalgesia remain largely underinvestigated. In the present study, we...
Background The mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle hyperalgesia remain largely underinvestigated. In the present study, we aimed to determine whether masseter muscle contraction induced by daily electrical stimulation influences the mechanical head-withdrawal threshold and genioglossus electromyography activity caused by the application of capsaicin to the upper first molar tooth pulp. We further investigated whether astroglial glutamine synthesis is involved in first molar tooth pulp hypersensitivity associated with masseter muscle contraction. Methods The first molar tooth pulp was treated with capsaicin or vehicle in masseter muscle contraction or sham rats, following which the astroglial glutamine synthetase inhibitor methionine sulfoximine or Phosphate buffered saline (PBS) was applied. Astroglial activation was assessed via immunohistochemistry. Results The mechanical head-withdrawal threshold of the ipsilateral masseter muscle was significantly decreased in masseter muscle contraction rats than in sham rats. Genioglossus electromyography activity was significantly higher in masseter muscle contraction rats than sham rats. Glial fibrillary acidic protein-immunoreactive cell density was significantly higher in masseter muscle contraction rats than in sham rats. Administration of methionine sulfoximine induced no significant changes in the density of glial fibrillary acidic protein-immunoreactive cells relative to PBS treatment. However, mechanical head-withdrawal threshold was significantly higher in masseter muscle contraction rats than PBS-treated rats after methionine sulfoximine administration. Genioglossus electromyography activity following first molar tooth pulp capsaicin treatment was significantly lower in methionine sulfoximine-treated rats than in PBS-treated rats. In the ipsilateral region, the total number of phosphorylated extracellular signal-regulated protein kinase immunoreactive cells in the medullary dorsal horn was significantly smaller upon first molar tooth pulp capsaicin application in methionine sulfoximine-treated rats than in PBS-treated rats. Conclusions Our results suggest that masseter muscle contraction induces astroglial activation, and that this activation spreads from caudal to the obex in the medullary dorsal horn, resulting in enhanced neuronal excitability associated with astroglial glutamine synthesis in medullary dorsal horn neurons receiving inputs from the tooth pulp. These findings provide significant insight into the mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle contraction.
Topics: Animals; Astrocytes; Capsaicin; Dental Pulp; Electric Stimulation; Electromyography; Extracellular Signal-Regulated MAP Kinases; Glial Fibrillary Acidic Protein; Glutamine; Hyperalgesia; Male; Masseter Muscle; Medulla Oblongata; Methionine Sulfoximine; Molar; Muscle Contraction; Phosphorylation; Posterior Horn Cells; Rats, Sprague-Dawley
PubMed: 29448913
DOI: 10.1177/1744806918763270 -
Brain Research Jul 1993This study provides evidence of catecholaminergic neurons in the cranial division of the parasympathetic nervous system. Presumptive catecholaminergic preganglionic...
This study provides evidence of catecholaminergic neurons in the cranial division of the parasympathetic nervous system. Presumptive catecholaminergic preganglionic neurons in the dorsal motor nucleus of the vagus (DMX) were revealed by a clearcut depletion of intracellular catecholamine-synthesizing enzyme immunoreactivity induced by unilateral cervical vagotomy and identified on tissues immunocytochemically processed for tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H) or phenylethanolamine N-methyltransferase (PNMT). This experimental design was essential because of the recent failure in two species to reproduce data previously obtained in double-label (combined immunocytochemical-retrograde transport) studies. Vagotomy data confirmed three spatially-segregated populations of catecholaminergic visceromotor neurons in the DMX. These cell bodies were morphologically identical to preganglionic neurons observed on alternate tissues stained for Nissl substance or immunostained for choline acetyltransferase (ChAT), the enzyme biosynthesizing acetylcholine. Neurons in the central and medial DMX demonstrated fall-off of TH-like immunoreactivity (LI) ipsilateral to the vagotomy at levels caudal to the obex. This cell group is assumed to be predominantly dopaminergic since relatively few neurons at this level of the DMX expressed D beta H-LI and none were immunostained for PNMT. A second population of immunoreactive neurons, concentrated in the rostral-lateral region of the DMX, was depleted of D beta H-LI on the ipsilateral side but did not express PNMT. These visceromotor neurons may, therefore, biosynthesize noradrenaline and belong to the rostral pole of the A2 area. A third population of presumptive adrenergic vagal dorsomotor neurons in the rostral-medial DMX was depleted of TH-, D beta H- and PNMT-LI at levels of the ipsilateral nucleus anterior to obex. Patterns of depletion of cytoplasmic enzyme-immunoreaction product were identical in all cases irrespective of the site of the transection or the postoperative survival period. Quantitative analysis demonstrated statistically significant loss of immunolabeled neurons in rostral and caudal subgroups of the DMX on the side ipsilateral to the vagotomy. It is concluded that catecholaminergic processes in the vagus nerve, as previously identified by the aldehyde-induced histofluorescence method, may partly arise from the lower brainstem.
Topics: Animals; Catecholamines; Immunohistochemistry; Male; Medulla Oblongata; Neck; Neurons; Rats; Rats, Sprague-Dawley; Vagotomy; Vagus Nerve
PubMed: 8374739
DOI: 10.1016/0006-8993(93)90607-o -
The Journal of Physiology Jun 19761. Electrophysiological techniques have been used to locate the origin of preganglionic vagal motoneurones supplying the heart of the cat. 2. The right cardiac vagal...
1. Electrophysiological techniques have been used to locate the origin of preganglionic vagal motoneurones supplying the heart of the cat. 2. The right cardiac vagal branches were identified anatomically and their ability to slow the heart was assessed by electrical stimulation. Control experiments revealed that contamination of cardiac branches by bronchomotor and oesophageal efferent fibres was likely to be small. 3. Fifty-seven neurones in the medulla were activated antidromically on stimulating the cardiac branches at up to 5 times the threshold for cardiac slowing. They had axons with conduction velocities between 3 and 15 m/sec, corresponding to B fibres. 4. None of these were located in the region of the dorsal motor nucleus of the vagus, in spite of repeated sampling there, but all were located in the region of the nucleus ambigus. Histological examination of marked neurones (forty-six of the fifty-seven neurones) revealed that they were associated with its principal column, rostral to the obex. 5. Sampling motoneurones of the dorsal motor nucleus revealed that most sent axons down the thoracic vagus below the cardiac branches. Only three of thirty-three could be activated antidromically by high intensity stimulation of the cardiac branches, but on the basis of their thresholds and conduction velocities, it is argued that they were unlikely to be cardio-inhibitory neurones. 6. It is concluded that preganglionic cardio-inhibitory neurones arise not in the dorsal motor nucleus, but in the principal column of the nucleus ambiguus.
Topics: Animals; Autonomic Fibers, Preganglionic; Axons; Cats; Electric Stimulation; Evoked Potentials; Female; Heart; Medulla Oblongata; Motor Neurons; Neural Conduction; Neurons, Efferent; Vagus Nerve
PubMed: 940054
DOI: 10.1113/jphysiol.1976.sp011414 -
The Journal of Physiology Dec 19711. Neuronal activity bearing a temporal relationship with spontaneous reticulo-ruminal movements was recorded with micro-electrodes from the medulla oblongata in...
1. Neuronal activity bearing a temporal relationship with spontaneous reticulo-ruminal movements was recorded with micro-electrodes from the medulla oblongata in halothane-anaesthetized sheep. Recording sites were located histologically after causing electro-coagulation at the micro-electrode tip.2. One hundred and forty-four gastric units were recorded from the dorsal vagal nucleus and up to 1 mm dorsal and lateral to the nucleus between transverse planes 1 mm caudal, and 4 mm rostral, to the obex. It is considered that records were obtained from the regions of cell bodies.3. The discharges of thirty-two vagal preganglionic motoneurones were identified by an antidromic collision technique. Conduction velocities ranged from 10-26 m/sec. They were located in the dorsal vagal nucleus and up to 0.5 mm dorsal and lateral to the nucleus. The majority of motoneurones innervated either the reticulum or the rumen. One ruminal unit discharged during both primary and secondary cycle movements.4. One hundred and twelve units which were not orthodromically or antidromically activated by stimulating the vagus nerves were considered to be interneurones. Four types were distinguishable on the basis of their patterns of discharge during primary cycle movements.5. The discharges of Type A interneurones resembled those of gastric motoneurones, having no resting discharge between contraction cycles. Their discharges were temporally related to either reticular contractions or rumen contractions during primary and secondary cycle movements.6. Types B and C interneurones have resting discharges which, respectively, increased and either decreased or stopped during each primary cycle movement.7. Discharges of only three units identified as interneurones resembled the discharges of gastric vagal afferent units.
Topics: Action Potentials; Animals; Electric Stimulation; Evoked Potentials; Gastrointestinal Motility; Interneurons; Medulla Oblongata; Microelectrodes; Motor Neurons; Neural Conduction; Neurons; Neurons, Afferent; Reticulum; Rumen; Sheep; Stomach; Vagus Nerve
PubMed: 5157594
DOI: 10.1113/jphysiol.1971.sp009679 -
Brain Research Nov 2009The anterior ethmoidal nerve (AEN) innervates the nasal passages and external nares, and serves as the afferent limb of the nasopharyngeal and diving responses. However,...
Unmyelinated fibers of the anterior ethmoidal nerve in the rat co-localize with neurons in the medullary dorsal horn and ventrolateral medulla activated by nasal stimulation.
The anterior ethmoidal nerve (AEN) innervates the nasal passages and external nares, and serves as the afferent limb of the nasopharyngeal and diving responses. However, although 65% of the AEN is composed of unmyelinated fibers, it has not been determined whether this afferent signal is carried by unmyelinated or myelinated fibers. We used the transganglionic tracers WGA-HRP, IB4-HRP, and CTB-HRP to trace the central projections of the AEN of the rat. Interpretation of the labeling patterns suggests that AEN unmyelinated fibers project primarily to the ventral tip of the ipsilateral medullary dorsal horn (MDH) at the level of the area postrema. Other unmyelinated projections were to the ventral paratrigeminal nucleus and ventrolateral medulla, specifically the Bötzinger and RVLM/C1 regions. Myelinated AEN fibers projected to the ventral paratrigeminal and mesencephalic trigeminal nuclei. Stimulating the nasal passages of urethane-anesthetized rats with ammonia vapors produced the nasopharyngeal response that included apnea, bradycardia and an increase in arterial blood pressure. Central projections of the AEN co-localized with neurons within both MDH and RVLM/C1 that were activated by nasal stimulation. Within the ventral MDH the density of AEN terminal projections positively correlated with the rostral-caudal location of activated neurons, especially at and just caudal to the obex. We conclude that unmyelinated AEN terminal projections are involved in the activation of neurons in the MDH and ventrolateral medulla that participate in the nasopharyngeal response in the rat. We also found that IB4-HRP was a much less robust tracer than WGA-HRP.
Topics: Analysis of Variance; Animals; Blood Pressure; Fluorescent Antibody Technique; Heart Rate; Image Processing, Computer-Assisted; Male; Medulla Oblongata; Microscopy, Fluorescence; Nasal Cavity; Nasopharynx; Nerve Fibers, Unmyelinated; Neural Pathways; Neuronal Tract-Tracers; Neurons; Odorants; Proto-Oncogene Proteins c-fos; Rats; Signal Processing, Computer-Assisted; Smell; Trigeminal Ganglion
PubMed: 19732757
DOI: 10.1016/j.brainres.2009.08.077 -
The Journal of Neuroscience : the... May 1988Local neural circuitry in the nucleus tractus solitarius (NTS) involved in cardiovascular control was studied by injecting nanoliter volumes of excitatory amino acids...
Local neural circuitry in the nucleus tractus solitarius (NTS) involved in cardiovascular control was studied by injecting nanoliter volumes of excitatory amino acids into the structure. Experiments were performed on urethane-anesthetized, artificially ventilated rats. Multibarrel micropipettes were used for pressure ejection of drugs or a dye for marking ejection sites. Ejected volumes, ranging from 200 pl to 25 nl, were directly monitored for every injection. Injections of as little as 200 fmol of L-glutamate in 200 pl into the medial and lateral NTS region rostral to the obex elicited marked, site-specific decreases in arterial pressure and heart rate. The majority of these responses were eliminated by blockade of parasympathetic and sympathetic neural outflow. At sites caudal to obex, in the commissural region of the NTS, L-glutamate injections produced marked elevations in heart rate and arterial pressure which were sympathetically mediated. Responses to L-glutamate were attenuated by concurrent injection of glutamic acid diethyl ester and DL-2-amino-4-phosphonobutyrate, or lidocaine. These results indicate a heterogeneity in the spatial organization of brain-stem circuitry underlying cardiovascular control that has not been previously described.
Topics: Animals; Atropine; Blood Pressure; Cardiovascular Physiological Phenomena; Cardiovascular System; Dose-Response Relationship, Drug; Electric Stimulation; Glutamates; Glutamic Acid; Heart Rate; Injections; Medulla Oblongata; Phentolamine; Propranolol; Rats
PubMed: 2896765
DOI: 10.1523/JNEUROSCI.08-05-01684.1988 -
The Journal of Physiology Nov 19711. Tooth pulp afferent fibres belonging exclusively to the Adelta group were stimulated bi-polarly with electrical pulses applied to the dentine and the central effects...
1. Tooth pulp afferent fibres belonging exclusively to the Adelta group were stimulated bi-polarly with electrical pulses applied to the dentine and the central effects of the stimulation were examined in the nucleus of the spinal trigeminal complex of anaesthetized cats.2. Field potentials evoked by single pulses to the upper or lower canine tooth pulp were explored over the nucleus of the spinal trigeminal tract in the region 5 mm caudally to the obex up to 8.5 mm rostrally to the obex. They were found to be restricted to a region of 5.5-8.5 mm rostrally to the obex, 4-5 mm laterally from the mid line, with a maximum amplitude at a depth of 5 +/- 0.5 mm.3. Antidromic action potentials were recorded from the tooth pulp afferents. The stimulating micro-electrode was inserted in the region of the medulla from which distinct field potentials could be recorded by orthodromic stimulation.4. Excitability of the central terminals of the tooth pulp primary afferents was increased when the test stimulus was preceded either by a conditioning volley in low threshold afferent fibres of the infraorbital nerve or in Adelta fibres of another tooth.5. Single pulses applied to the afferent fibres of the tooth pulp produced changes in the excitability of central terminals of the fast conducting afferent fibres of the infraorbital nerve.6. The greatly increased excitability of central terminals of tooth pulp primary afferent fibres was accompanied by a small decrease in their synaptic efficiency as estimated from the changes of the post-synaptic component of the field potential evoked by their stimulation.7. It is concluded that an analogous presynaptic control mechanism is present at the central terminals of the tooth pulp primary afferent fibres as is known for the fast conducting cutaneous system. But a difference in the specifity of the action from this afferent system is suggested. While activity from Aalpha fibres is very effective in evoking primary afferent depolarization at both fast conducting trigeminal fibres and slow conducting Adelta system, the Adelta fibre activity is effective only at the latter, and not at the former.
Topics: Action Potentials; Animals; Brain Stem; Cats; Dental Pulp; Electric Stimulation; Electrophysiology; Evoked Potentials; Nerve Endings; Neurons; Neurons, Afferent
PubMed: 5133947
DOI: 10.1113/jphysiol.1971.sp009631 -
The Journal of Physiology Jun 19941. The relationship between ventilatory acclimatization to chronic hypoxia (10% O2-90% N2) and noradrenaline metabolism was examined in two regions located immediately... (Comparative Study)
Comparative Study
1. The relationship between ventilatory acclimatization to chronic hypoxia (10% O2-90% N2) and noradrenaline metabolism was examined in two regions located immediately caudal and rostral to the obex within the rat solitary complex. 2. Three experimental protocols were established. In protocol 1, the percentage changes in respiratory tidal volume, frequency and minute ventilation elicited by 4, 7, 10 and 14 days of hypoxia were assessed by flow plethysmography in awake rats, and then the content of tyrosine hydroxylase was measured in the solitary complex. In protocol 2, the time course response of tyrosine hydroxylase protein level was determined after 3, 7, 14 and 22 days of hypoxia by using a quantitative immunoblotting method for the protein assay. In protocol 3, the turnover of noradrenaline was estimated in the solitary complex after 14 days of hypoxia. 3. A progressive increase in ventilation was observed to reach a maximum (+105 +/- 15%, mean +/- S.E.M.) above normoxic control after 10 days of hypoxia, at which time it stabilized. Furthermore, tyrosine hydroxylase protein increased progressively and reached a maximal level at 14 days of hypoxia (+36 +/- 4%, mean +/- S.E.M.). Return to the basal level of tyrosine hydroxylase was observed after 22 days of hypoxia. 4. Tyrosine hydroxylase content (+36 +/- 4%) and noradrenaline turnover (+394 +/- 3%) increased exclusively in the caudal part of the solitary complex. 5. The ventilatory acclimatization to chronic hypoxia preceded the increase in tyrosine hydroxylase and these two parameters were significantly correlated. 6. These data suggest that ventilatory acclimatization to chronic hypoxia is associated with topical modifications of the brainstem catecholamine metabolism.
Topics: Acclimatization; Animals; Hypoxia; Male; Norepinephrine; Rats; Rats, Sprague-Dawley; Respiration; Solitary Nucleus; Tyrosine 3-Monooxygenase
PubMed: 7932223
DOI: 10.1113/jphysiol.1994.sp020194 -
Physiological Research 2000We have tested the hypothesis that neurons of both the ventral reticular nucleus and the adjacent parts of the lateral tegmental field (LTF) may be important for the...
We have tested the hypothesis that neurons of both the ventral reticular nucleus and the adjacent parts of the lateral tegmental field (LTF) may be important for the production of motor programs associated with cough, expiration and aspiration reflexes. Our studies were conducted on non-decerebrate, spontaneously breathing cats under pentobarbitone anesthesia. Dysfunction of the medullary LTF region above the obex, produced by uni- or bilateral injections of kainic acid (a neurotoxin), regularly abolished the cough reflex evoked by mechanical stimulation of both the tracheobronchial and laryngeal regions and in most cases also the expiration reflex induced from the glottal area. However, some electrical activity still occurred in the neurogram of the recurrent laryngeal nerve during probing the laryngeal and glottal regions. Interestingly, the aspiration reflex elicited from the nasopharynx regularly persisted, although with lower intensity after the LTF lesion. Nevertheless, successive midcollicular decerebration performed in four cats also abolished the aspiration reflex. These experiments demonstrate the importance of medullary LTF neurons for the normal occurrence of cough and expiration reflexes. One possible explanation for the elimination of these expulsive processes is that the blockade of the LTF neurons may remove an important source of a facilitatory input to the brainstem circuitries that mediate cough and expiration reflexes. In addition, the potential importance of the mesencephalic reticular formation for the occurrence of the aspiration reflex and the role of the LTF in modulating both the eupnoeic breathing and the blood pressure are also discussed.
Topics: Anesthesia; Animals; Blood Pressure; Cats; Cough; Decerebrate State; Electromyography; Excitatory Amino Acid Agonists; Female; Fourth Ventricle; Kainic Acid; Male; Medulla Oblongata; Mesencephalon; Nerve Degeneration; Physical Stimulation; Reflex; Respiratory Mechanics; Reticular Formation
PubMed: 11043927
DOI: No ID Found