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W M St John

Publications and source records attributed to W M St John.

At least 19 recordsLinked to original sources
PubMed1999

Rostral medullary respiratory neuronal activities of decerebrate cats in eupnea, apneusis and gasping.

Eupnea is generated by mechanisms within the pons and medulla. Following removal of pons or exposure to anoxia, gasping is elicited. Eupnea and gasping are markedly different ventilatory patterns. The genesis of gasping is dependent upon rostral medullary neuronal activities. To generate the gasp, these activities should commence before the phrenic burst. In decerebrate, vagotomized, paralyzed and ventilated cats, eupnea was altered to gasping in anoxia. Rostral medullary neuronal activities had inspiratory, expiratory and phase-spanning patterns in eupnea. During gasping, some inspiratory neuronal activities commenced before the phrenic gasp; these same neurons had commenced activities after the onset of the eupneic phrenic burst. Expiratory and phase-spanning neurons did not discharge. Neuronal activities which are consonant with a role in the neurogenesis of gasping had very different discharge patterns in eupnea. Results support the concept that medullary mechanisms for gasping are incorporated in the ponto-medullary circuit responsible for the neurogenesis and expression of eupnea.

Animals↗
PubMed1998

Pontine cholinergic respiratory depression in neonatal and young rats.

We postulated that activation of pontine cholinergic mechanisms would cause respiratory depression in neonatal and young rats. Phrenic activity was recorded in decerebrate, paralyzed, ventilated and vagotomized rats of 4 to 22 days after birth. Small volumes (10-60 nl) of carbachol (44-88 mM) were injected into the medial portion of the rostral pons. The injection of carbachol, but not saline, decreased phrenic peak activity (83 +/- 6% of control) and respiratory frequency (64 +/- 9.5% of control) within 2 min following the injection in neonates and the depression lasted for less than 10 min. The site of injection in the pontine reticular formation was confirmed by histology. Results suggest that cholinergic mechanisms in the medial pons depress respiratory activity in the neonate.

Animals↗
PubMed1997

Lesions of regions for in vitro ventilatory genesis eliminate gasping but not eupnea.

Medullary regions, termed 'pre-inspiratory' and 'pre-Bötzinger', are considered critical for the neurogenesis of rhythmic ventilatory activity of in vitro preparations of the neonatal rat. We examined the influence of destruction of neurons in these regions, by microinjections of kainic acid, upon eupnea and gasping in vivo. Decerebrate, vagotomized, paralyzed and ventilated rats of age 8-15 days were used; the phrenic nerve activity was recorded. Eupnea was not consistently altered following destruction of neurons in any region. However, in the majority of animals, anoxia-induced gasping was not observed following injections of kainic acid into the 'pre-inspiratory' region, 'pre-Bötzinger' complex or lateral tegmental field; the latter region is important for the neurogenesis of gasping in adults. Injections into other regions did not prevent the elicitation of gasping. These results do not support the possibility that neuronal activities which are responsible for respiratory rhythm generation in vitro underlie the neurogenesis of eupnea in vivo.

Animals↗
PubMed1997

The morphology and connections of neurons in the gasping centre of adult rats.

Neuronal activities in the intermediate reticular nucleus and adjacent lateral tegmental field are critical for the neurogenesis of the ventilatory pattern of gasping. We report herein the anatomical features of these neurons, their axonal projections and the location of neurons providing afferent inputs. These neuroanatomical evaluations were performed by iontophoretic injection of the tracer Neurobiotin into the region of the intermediate reticular nucleus of the rat. At the site of injection, neurons having soma of 30-50 microns were filled. Labelled axons and terminals were observed in ipsilateral regions which contain neurons having established functions in the control of ventilatory activity. These regions include the nucleus ambiguous and motor nuclei of the hypoglossal and facial nerves. In addition, axonal projections extended to the contralateral region of the intermediate reticular nucleus. From this contralateral region, retrograde tracing revealed projections to the site of injection. Similarly, many ipsilateral regions which received axonal terminals from the region of the intermediate reticular nucleus had reciprocal projections to this region. These anatomical results support the physiological observation that the neurogenesis of gasping involves a synchronized activation of diverse components of the brainstem ventilatory control system.

Animals↗
PubMed1996

Characterizations and comparisons of eupnoea and gasping in neonatal rats.

1. Our purpose was to characterize the ventilatory patterns of eupnoea and gasping in the neonatal rat. This study was precipitated by reports, using in vitro brainstem spinal cord preparations, that only a single pattern is present in neonatal rats. 2. In anaesthetized or decerebrate rat pups aged less than 13 days, eupnoea was characterized by a sudden onset of inspiratory activity and then a more gradual rise to peak levels. Following vagotomy, frequency fell and peak phrenic activity and tidal volume increased. The rate of rise of inspiratory activity also rose, but peak levels were still achieved during the latter half of inspiration. Vagal efferent activity exhibited bursts during both inspiration and the early expiration. This basic eupnoeic rhythm was not altered after sectioning of the carotid sinus nerves. 3. Upon exposure to hypoxia or anoxia, phrenic activity, tidal volume and frequency initially increased and then declined. In many animals, ventilatory activity then ceased, but later returned with a gasping pattern. 4. Gasping was characterized by a sudden onset of phrenic activity, which reached a peak intensity during the early portion of inspiration. The expiratory burst of vagal activity was eliminated. 5. Reductions of body temperature from 37 to 27 degrees C resulted in prolongations of inspiration and expiration and decreases of phrenic amplitude; phasic phrenic activity completely disappeared in some animals. Upon exposure to anoxia, gasping was observed, even in animals in which phrenic activity had disappeared in hyperoxia. 6. We conclude that, from the day of birth, rats can exhibit eupnoea and gasping patterns which are very similar to those of adult animals. 7. The rhythmic neural activities of the in vitro brainstem-spinal cord preparation, reported by others, differ markedly from eupnoea but are identical with gasping. We therefore conclude that this preparation is not suitable for investigation of the mechanisms that generate eupnoeic breathing.

Age Factors↗
PubMed1996

Characterization of ventilatory responses to hypoxia in neonatal rats.

Newborn animals exhibit a biphasic response to hypoxia, with ventilation increasing and then declining. Our purpose was to define if this response could be supported by the pontile and medullary respiratory centers. Spontaneously breathing and paralyzed and ventilated decerebrate or anesthetized, vagotomized rats were studied from birth to 13 days thereafter. Peak integrated phrenic activity, or tidal volume, and frequency initially increased and then declined after inspired oxygen was reduced from hyperoxic to hypoxic levels; most animals became apneic in hypoxia. Apnea occurred in a greater proportion of animals and more quickly with more severe hypoxia. Following sectioning of the carotid sinus nerves, ventilatory activity declined with a change from hyperoxia to normoxia. We conclude that the biphasic ventilatory response to hypoxia represents a balance between synaptically-induced augmentations and reductions of brainstem neuronal activities. The carotid chemoreceptors play a fundamental role in the augmentations, and reductions appear dependent upon actions of hypoxia upon brainstem mechanisms.

Anesthesia↗
PubMed1996

Medullary regions for neurogenesis of gasping: noeud vital or noeuds vitals?

Gasping is a critical mechanism for survival in that it serves as a mechanism for autoresuscitation when eupnea fails. Eupnea and gasping are separable patterns of automatic ventilatory activity in all mammalian species from the day of birth. The neurogenesis of the gasp is dependent on the discharge of neurons in the rostroventral medulla. This gasping center overlaps a region termed "the pre-Bötzinger complex." Neuronal activities of this complex, characterized in an in vitro brain stem spinal cord preparation of the neonatal rat, have been hypothesized to underlie respiratory rhythm generation. Yet, the rhythmic activity of this in vitro preparation is markedly different from eupnea but identical with gasping in vivo. In eupnea, medullary neuronal activities generating the gasp and the identical rhythm of the in vitro preparation are incorporated into a portion of the pontomedullary circuit defining eupneic ventilatory activity. However, these medullary neuronal activities do not appear critical for the neurogenesis of eupnea, per se.

Animals↗
PubMed1995

The functional expression of a pontine pneumotaxic centre in neonatal rats.

1. Our purpose was to determine whether a pneumotaxic centre could be localized to the rostral pons in newborn rats. We recorded efferent activity of the phrenic nerve in decerebrate, paralysed, vagotomized and ventilated rats, whose age varied from the day of birth to 22 days. 2. The rostral pontine tegmentum was ablated by aspiration and electrolytic lesions. Neuronal activities were blocked by microinjections of the glutamate antagonist MK-801 and were destroyed by the neurotoxins kainic acid and domoic acid. 3. Unilateral ablation or lesions of the pontine tegmentum caused a significant prolongation of the duration of the phrenic burst in animals of all ages. This duration increased further following contralateral destruction and apneusis was established. The period between phrenic bursts increased in most rats whereas peak phrenic height was not consistently altered. 4. Similar changes to those following physical ablations or lesions were recorded after microinjections of MK-801 or neurotoxins. 5. A common region of ablation, lesion and microinjection was the parabrachialis and Köllicker-Fuse nucleus. 6. Exposure to anoxia resulted in an alteration from apnoeusis to gasping. 7. We conclude that from the day of birth, rostral pontine pneumotaxic mechanisms play a significant role in the definition of eupnoea. Moreover, from the day of birth, rats can exhibit the classical ventilatory patterns of eupnoea, apneusis and gasping.

Age Factors↗
PubMed1995

Power spectral analysis of respiratory responses to pharyngeal stimulation in cats: comparisons with eupnoea and gasping.

1. Based on similarities between properties of gasping and the aspiration reflex, we hypothesized that this reflex activates the central pattern generator for gasping. To evaluate this hypothesis, we have analysed high-frequency oscillations in phrenic and hypoglossal neural activities. These oscillations, analysed by power and coherence spectra, are considered as signatures of the central pattern generators for automatic ventilatory activity. 2. In decerebrate, vagotomized, paralysed and ventilated cats, the aspiration reflex was elicited in eupnoea and gasping by mechanical stimulation of the pharynx and electrical stimulation of the glossopharyngeal nerve. 3. Compared with eupnoeic values, the peaks in the power spectra occurred at higher frequencies in spontaneous gasping. Peaks in the coherence spectra showed identical changes. 4. Power and coherence spectra of inspiratory neural activities during the aspiration reflex differed markedly from those of eupnoea, but were similar to those in gasping. 5. We conclude that mechanical stimulation of the pharynx or electrical stimulation of the glossopharyngeal nerve activates a reflex by which the central pattern generator for eupnoea is depressed, and that for gasping is activated. Our results also support the concept that separate brainstem mechanisms generate ventilatory activity in eupnoea and gasping.

Animals↗
PubMed1995

Expiratory neural activities in gasping induced by pharyngeal stimulation and hypoxia.

The purpose was to characterize expiratory neural activities in gasping elicited during the aspiration reflex (AR) in hyperoxia and during hypoxia-induced gasping. In decerebrate, vagotomized and paralyzed cats, we recorded activities of inspiratory and expiratory cranial and spinal nerves. The AR was elicited by touching the epipharyngeal mucosa. In eupnea, spinal expiratory activities were greatly decreased during AR whereas laryngeal expiratory activities were increased. In hypoxia-induced gasping, both the laryngeal and spinal expiratory activities were reduced. All of the inspiratory activities were increased during both gasping and the AR. In addition, neural activities were below control levels following AR; activities gradually recovered to control levels. We conclude that spinal expiratory activities are inhibited during the AR and gasping. Results are consistent with the concept that medullary mechanisms for gasping are recruited by mechanical stimulation of the epipharynx. In hypoxia-induced gasping, the hypoxia, per se, causes a separate suppression of laryngeal expiratory activities.

Animals↗
PubMed1995

Medullary neuronal activities in gasping induced by pharyngeal stimulation and hypoxia.

We examined the hypothesis that medullary respiratory-related and non-respiratory-related neuronal activities are similarly altered with the "aspiration reflex", induced by mechanical stimulation of the epipharyngeal mucosa, and gasping, induced by severe hypoxia. Extracellular neuronal activities were recorded in decerebrate, paralyzed and ventilated cats. Phrenic activity and neuronal activities were monitored in eupnea and gasping. Seventy-one unit activities were recorded in the lateral medulla including the nucleus tractus solitorii (NTS), lateral tegmental field (LTF) and the nucleus ambiguus (NA). The respiratory modulation of a neuronal activity was quantified by a eta 2 statistic (Orem, J. and Dick, T., 1983, J. Neurophysiol. 50: 1098-1107). The eta 2 values of the units ranged from 0.02 to 0.93. Inspiratory-related activities with relative high eta 2 values (n = 16) were recorded in the region closed to the NTS. Phase-spanning (n = 7) and expiratory-related activities (n = 10) were recorded in the ventral medullary region. Units with low eta 2 values (n = 29) and with no spontaneous activity (n = 9) in eupnea were recorded in the region of the LTF. In both "aspiration reflex" and gasping, inspiratory-related activities were augmented and expiratory-related activities were suppressed. Tonic units were activated and additional activities were recruited. The modulation of the neuronal activities to gasping induced by anoxia was identical to that induced by pharyngeal stimulation in either hyperoxia or severe hypoxia. We concluded that medullary gasping mechanism is recruited by pharyngeal stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Medullary loci critical for expression of gasping in adult rats.

1. Our purpose was to define whether a region of medulla could be identified that is critical for the expression of gasping. 2. Decerebrate, vagotomized, paralysed and ventilated adult rats were used. The pattern of phrenic activity was reversibly altered from eupnoea to gasping by exposure to hypoxia or anoxia. 3. Gasping was irreversibly eliminated following unilateral electrolytic lesions of the lateral tegmental field of the medulla. The eupnoeic rhythm continued after these lesions. 4. Injections of kainic acid into the lateral tegmental field also eliminated gasping. Phrenic activity in eupnoea was not altered. 5. Lesions outside the lateral tegmental field caused marked changes in the eupnoeic rhythm, including expiratory apnoea. Upon exposure to hypoxia or anoxia, gasping was still induced. 6. This region for the neurogenesis of gasping in rats is identical to the region that serves a comparable function in cats. Moreover, it overlaps with the 'pre-Bötzinger' complex which has been described for the in vitro brainstem preparation of the neonatal rat. Our results raise doubts that this complex plays a role in the neurogenesis of eupnoea.

Animals↗
PubMed1994

Reflex recruitment of medullary gasping mechanisms in eupnoea by pharyngeal stimulation in cats.

1. Mechanical stimulation of the naso- and oropharynx causes the replacement of the eupnoeic ventilatory pattern by a brief, but large, burst of activity of the phrenic nerve. Our purpose was to define whether these changes in phrenic activity represent a switch to gasping. 2. In decerebrate, vagotomized, paralysed and ventilated cats, mechanical stimulation of the pharynx was performed during eupnoea, apneusis and gasping. The latter two ventilatory patterns were produced by ventilating the experimental animal with 1.0% carbon monoxide in air or with 100% nitrogen. Eupnoea could be re-established by a recommencement of ventilation with oxygen. 3. The rate of rise of phrenic activity and its peak height were much greater following mechanical stimulation of the pharynx than the phrenic bursts of eupnoea or apneusis. The durations of phrenic burst and the period between these were much less following pharyngeal stimulation. In contrast, these variables of phrenic activity were the same during pharyngeal stimulation and in gasping. 4. Previous studies had established that activity within a region of the lateral tegmental field of medulla is critical for the manifestation of gasping. Hence, electrical stimulation of this region during gasping elicits premature gasps whereas its ablation irreversibly eliminates gasping. 5. We positioned a multibarrelled pipette in the critical medullary region for gasping. Its location was verified, once gasping was established in hypoxia or anoxia, by the elicitation of premature gasps following electrical stimulation. Neurons in this region were destroyed by microinjections of the neurotoxin kainic acid; in a few experiments the region was destroyed by electrolytic lesions. 6. Following destruction of the region of the lateral tegmental field, gasping could no longer be provoked in anoxia. In contrast, the eupnoeic pattern of phrenic activity continued. However, mechanical stimulation of the pharynx no longer caused any changes in the on-going pattern of phrenic activity. 7. We conclude that mechanical stimulation of the pharynx elicits a powerful reflex by which eupnoea is suppressed and gasping is elicited. Stated differently, the changes in phrenic activity during this pharyngeal stimulation in fact represent gasps. 8. Gasps are dependent upon activity within a region of the lateral tegmental field of the medulla. This region plays no role in the neurogenesis of eupnoea. Hence, our results provide additional support for the concept that there are multiple sites for ventilatory neurogenesis in the mammalian brainstem.

Animals↗
PubMed1994

Electrical stimulation of pneumotaxic center: activation of fibers and neurons.

Electrical stimulations of the pneumotaxic center can result in a phase-switch from neural inspiration to expiration or the reverse. Terminations of inspiration are also obtained from many loci ventral to the pneumotaxic center. We hypothesized that responses to some stimulations reflect an activation of fibers rather than neurons. Studies were conducted in decerebrate, vagotomized, paralyzed and ventilated cats. Activities of the phrenic and triangularis sterni nerves were recorded. A multibarreled pipette was inserted into the rostral pons. Electrical stimulation was delivered through two barrels; another contained kainic acid to destroy neurons. The threshold current for producing inspiratory termination was not altered in most regions following the injections of kainic acid. However, stimulation of neurons did appear to underlie the premature onset of phrenic activity. In addition, neurons in medial pontile regions regulate triangularis sterni activity. We conclude that some functions ascribed to the pneumotaxic center are, in fact, subserved by neurons in other regions of the central nervous system.

Animals↗
PubMed1994

Separation of multiple functions in ventilatory control of pneumotaxic mechanisms.

Multiple functions have been ascribed to the pontile pneumotaxic center. We hypothesized that these functions might be separable among neurons in different regions. In decerebrate, vagotomized, paralyzed and ventilated cats, activities of the phrenic and triangularis sterni nerves were recorded. Microinjections of kainic acid were used to destroy neurons. Neurons in the rostrolateral tegmentum at the ponto-mesencephalic border controlled the duration of neural inspiration. Expiratory duration was controlled by neurons in the more caudal nucleus parabrachialis medialis and Kolliker-Fuse nucleus. Ventilatory responses to hypercapnia were depressed following injections of kainic acid into regions controlling either inspiratory or expiratory durations. The phases of expiration were regulated by two groups of neurons, located medial and lateral in the rostral pons. We conclude that rostral pontile and mesencephalic mechanisms control multiple aspects of the eupneic ventilatory cycle. There mechanisms are served by neurons in separable anatomical regions.

Animals↗
PubMed1994

Involvement of pontile NMDA receptors in inspiratory termination in rat.

We evaluated the hypothesis that N-methyl-D-aspartate (NMDA) receptors in the rostral pons mediate the off-switch of inspiration in the adult rat. Experiments were performed on decerebrate, vagotomized, paralyzed and ventilated animals. Activity of phrenic nerve was recorded. Small volumes (10 nl) of NMDA antagonists, MK-801 and AP-5, or non-NMDA antagonists, CNQX and DNQX, were injected into the rostral pons. We found that injections of MK-801 reversibly increased the duration of neural inspiration (TI), and the increase was dose-dependent. Injections of AP-5 also increased TI. Injections of the DNQX and CNQX in these same loci resulted in no significant changes in the duration of neural inspiration, expiration or peak phrenic activity (PNA). However, injections of kainic acid (KA, 4.7 mM) in the loci increased TI and decreased PNA. We conclude that neurons regulating the off-switch mechanism are located in the rostral pons. Further, the binding of NMDA receptors in the rostral pons is involved in this off-switch mechanism.

2-Amino-5-phosphonovalerate↗
PubMed1993

Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus to CO2.

We hypothesized that the retrotrapezoid nucleus (RTN) contains both respiratory modulated (RM) and non-respiratory modulated (NRM) neurons which participate in the ventilatory response to increased CO2. We made extracellular recordings of the activity of 46 single units in the RTN of 9 decerebrate, paralyzed, ventilated cats (5 intact; 4 with carotid body and sinus ablation) under eucapnic (PCO2 = 34.2 +/- 3.5 mmHg; mean +/- SD) and hypercapnic (PCO2 = 47.4 +/- 3.4 conditions. To define a RM unit, we used the eta 2 statistic which is the ratio of the variance of the unit firing rate within respiratory cycles to that across respiratory cycles. We classified the units as RM (N = 17) if the eta 2 values in eucapnia or hypercapnia were > or = 0.25 and as NRM (N = 29) if the values were < 0.25. Overall, 19/46 units (41%) increased their firing rate with increased CO2, 5 decreased their firing rate, and 22 had no significant change in firing rate. Of 17 RM units, 8 (47%) increased their mean firing rate with hypercapnia from 7.6 +/- 3.9 to 23.2 +/- 6.8 spikes/sec. These included 5 inspiratory units, 2 inspiratory units that had an onset of firing in late expiration (Pre-I/I), and 1 expiratory unit. Seven of these also changed their discharge pattern (eucapnic eta 2 = 0.02 to 0.12; hypercapnic eta 2 = 0.34 to 0.79) Of 29 NRM units, 11 (38%) showed a significant increase in mean firing rate with CO2 stimulation from 19.8 +/- 7.2 to 31.3 +/- 8.2 spikes/sec. The RTN has RM units which change their discharge pattern and firing rate in response to increased CO2, as do units within the medulla and pons, and it has NRM units which are also responsive to increased CO2. These data indicate that some neurons of the RTN are involved in the central chemoreceptor response but they provide no direct evidence that chemoreception resides within the RTN.

Animals↗