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Biomedical subjects

K M Spyer

Publications and source records attributed to K M Spyer.

At least 109 records · Page 6Linked to original sources

Presynaptic depolarization in myelinated vagal afferent fibres terminating in the nucleus of the tractus solitarius in the cat.

The presynaptic influences that act on terminals of slowly adapting lung stretch receptor afferents and aortic baroreceptor afferents within the nucleus of the solitary tract were assessed using intracellular recording and antidromic stimulation techniques. Central respiratory influences on the excitability of lung stretch receptor terminals were observed in 29% (4 of 14) of measurements. These were confirmed in intracellular recordings where membrane depolarizations in synchrony with phrenic nerve discharge were seen in 17% (4 of 24) of fibres. In three cases membrane depolarization also occurred synchronously with artificial lung inflation. Neither tests of excitability nor intracellular recording revealed any evidence for equivalent presynaptic influences on 16 myelinated aortic baroreceptor terminals. Stimulation of the superior laryngeal nerve evoked depolarizations in 50% (7 of 14) of lung stretch receptor terminals. These took the form of complex waves of depolarization with both short (3-8 ms) and long latency (27-35 ms) components. The amplitude of the long latency response increased during the period of phrenic nerve discharge, i.e. during "central inspiration". These effects are discussed in relation to the central respiratory influences on both respiratory and cardiovascular reflexes.

Animals↗

Discharge patterns of cervical sympathetic preganglionic neurones related to central respiratory drive in the rat.

The central respiratory-drive-related inputs to antidromically identified cervical sympathetic preganglionic neurones have been investigated, in the rat, using extracellular recording techniques, the ionophoretic application of an excitatory amino acid (glutamate) to increase their excitability, and phrenic nerve discharge as an indicator of central respiratory drive. Three distinct firing patterns of sympathetic preganglionic neurones are described: maximal discharge during phrenic nerve activity, maximal discharge during phrenic silence, and a firing pattern unrelated to phrenic nerve discharge. Both spontaneously active and glutamate-activated silent cervical sympathetic preganglionic neurones had similar, if not identical, firing patterns. The application of glutamate, using ionophoretic currents of up to 100 nA, did not disrupt central respiratory-drive-related discharge patterns indicating that these inputs are an important contribution in the regulation of the firing pattern of a proportion of sympathetic preganglionic neurones. On the basis of these observations it is proposed that some sympathetic preganglionic neurones may receive central respiratory drive potentials similar to those received by respiratory motoneurones.

Action Potentials↗

Amygdaloid influences on brain-stem neurones in the rabbit.

1. Electrical stimulation of the central nucleus of the amygdala in the urethane or alpha-chloralose anaesthetized rabbit evokes a bradycardia with a rapid onset and a concomitant fall in arterial blood pressure. 2. Extracellular neuronal activity was recorded in the ipsilateral nucleus tractus solitarius and dorsal vagal nucleus whilst stimulating the ipsilateral central nucleus of the amygdala, the aortic and vagus nerves. 3. A total of 213 neurones were activated by stimulation of at least one of these inputs. 93 of these neurones received a marked excitatory input from the central nucleus with a wide range of latencies (2-100 ms). 50 of these cells also received inputs from either the aortic or vagus nerves, or both. 4. The activity of 42 vagal preganglionic neurones was recorded in the dorsal vagal nucleus of which 22 had properties typical of cardioinhibitory neurones. 9 of these vagal motoneurones received inputs from the central nucleus with latencies between 2 and 100 ms. Of these, 5 had physiological properties indicating they were cardio-inhibitory neurones. 5. We conclude that neurones in the nucleus tractus solitarius and dorsal vagal nucleus can be influenced by descending inputs arising from the central nucleus of the amygdala. Some of these neurones are also likely to be influenced by afferents innervating the thoracic viscera and arterial baroreceptors. The implications of these observations on the role of forebrain-brain-stem interactions in cardiovascular control are discussed.

Action Potentials↗

The localization of adrenoceptors and opiate receptors in regions of the cat central nervous system involved in cardiovascular control.

The distribution of adrenoceptors and opiate receptors in the nucleus of the tractus solitarius and the intermediolateral cell column of the thoracic spinal cord of the cat have been investigated using an in vitro autoradiographic technique. Specific binding of [3H]yohimbine and [3H]rauwolscine (alpha 2-adrenoceptor ligands) was seen within the intermediolateral cell column but no obvious binding of [3H]prazosin, an alpha 1-ligand, was observed. No evidence of a significant population of opiate receptors was obtained in the intermediolateral cell column. Within the nucleus of the tractus solitarius a marked binding of [3H]yohimbine and [3H]rauwolscine was accompanied, however, by a more restricted binding of [3H]naloxone and [3H]dihydromorphine indicating the presence of both alpha 2-adrenoceptors and opiate receptors. As with the intermediolateral cell column no evidence of [3H]prazosin binding was seen. These observations may have particular relevance for the physiology and pharmacology of cardiovascular control. In the case of the intermediolateral cell column it is consistent with evidence of a catecholamine innervation originating from the brainstem. With regard to the nucleus of the tractus solitarius the location of the receptor groups is discussed in the light of the anatomy and physiology of its afferent innervation.

Animals↗

Post-synaptic activity evoked in the nucleus tractus solitarius by carotid sinus and aortic nerve afferents in the cat.

Post-synaptic responses evoked in neurones of the nucleus tractus solitarius by electrical stimulation of the carotid sinus, aortic and vagal nerves, alone or in combination, have been studied in anaesthetized cats using both extracellular and intracellular recording techniques. A total of 292 neurones received an input from at least one of the three nerves tested. The activity of the large majority of these cells (249) could only be shown to be altered by stimulation of one of these nerves and in 222 of these cases this was an excitatory response. These responses showed the expected post-synaptic characteristics including temporal summation and, in intracellular records, a summation of evoked excitatory post-synaptic potentials (e.p.s.p.s). The minimum latency to onset of these responses was variable, both for individual cells and for the population as a whole and varied within the range 2-124 ms. In a small number of cells (twenty-seven), the input was purely inhibitory in nature. In neurones showing a tonic discharge this produced a decrease in the rate of firing. This influence was most marked in intracellular records where membrane hyperpolarizations were noted. Again, the latency to onset was variable, in the range 4-27 ms. Convergent inputs from two or more of the nerves were identified in forty-three neurones. The effects of these were always excitatory. They could be observed both as a facilitation of spike activity recorded extracellularly and as summation of subliminally evoked e.p.s.p.s recorded intracellularly. On the basis of threshold voltages and latency to onset, the afferents to these neurones are indistinguishable from those providing an exclusive input. It can be concluded that at least some of the neurones in the nucleus tractus solitarius and its vicinity receive inputs from more than one source. The implications of these observations on the role of this brain-stem area in cardiorespiratory reflexes is discussed.

Action Potentials↗

Excitatory effects of iontophoretically applied substance P on neurons in the nucleus tractus solitarius of the cat: lack of interaction with opiates and opioids.

The effects of iontophoretically applied substance P (SP), (D-Pro2, D-Trp7,9)-SP and (D-Pro4, D-Trp7,9,10)-SP were studied on neurons identified by their histological location in the nucleus tractus solitarius (NTS), their response to vagal or carotid sinus nerve stimulation and eventually their functional correlation with the central respiratory drive. Potent and consistent excitatory effects of SP were found supporting its role as a putative excitatory transmitter in the NTS. The effects of SP and L-glutamate (Glu) were differentiated by the relative insensitivity of SP-induced excitations to levorphanol and Met-enkephalin.

Animals↗

Evidence for a monosynaptic connection between slowly adapting pulmonary stretch receptor afferents and inspiratory beta neurones.

The synaptic connection between slowly adapting pulmonary stretch receptor afferents and inspiratory neurones within a region ventral to the tractus solitarius was determined using intracellular recording and spike triggered averaging techniques. When the vagus nerve was stimulated at intensities eliciting a Hering-Breuer reflex, the difference in mean latency between centrally recorded action potentials of slowly adapting pulmonary stretch receptor afferents and e.p.s.p.s of inspiratory beta neurones was 0.2 ms. This difference is indicative of a monosynaptic connection. Extracellular single unit spikes of slowly adapting pulmonary stretch receptors recorded from the nodose ganglion were used to trigger the averaging of synaptic noise recorded from inspiratory neurones. A prominent wave of synaptic depolarization was observed in all inspiratory beta neurones even when a small number of sweeps were averaged. This depolarization was absent from inspiratory alpha neurones. The shape indices of these depolarizations are consistent with a monosynaptic connection between slowly adapting pulmonary stretch receptor afferents and inspiratory beta neurones. In addition, the data raise the possibility that this connection is multiple and distributed.

Animals↗

The central projections of carotid baroreceptors and chemoreceptors in the cat: a neurophysiological study.

The medullary projections of afferent neurons with cell bodies in the petrosal ganglion have been investigated using an antidromic mapping technique. Of the ninety-three units studied, fifty-eight were shown to have patterns of discharge indicating that they were baroreceptors and thirty-five showed responses to stimuli indicating that they were arterial chemoreceptors. Twelve baroreceptor and thirteen chemoreceptor afferents had sufficiently stable unitary discharges to permit a detailed estimation of some of their central projections using stimulation through monopolar tungsten micro-electrodes to evoke antidromic spikes. In order to estimate their pattern of projection, depth-threshold contours for each penetration through the dorsomedial medulla and the values of antidromic latency were considered. Baroreceptor afferent fibres with myelinated (six units) and non-myelinated (six units) axons showed similar patterns of central projection. All could be activated from the ipsilateral nucleus of the tractus solitarius (n.t.s.), most often from its lateral divisions rostral to the obex. The dorsolateral and dorsomedial portions of the n.t.s. were most often innervated, with the commissural subnucleus receiving an innervation in seven of the twelve neurones studied. Stimulation of the ventrolateral subnucleus was effective in activating two afferent fibres whilst stimulation of the ventral subnucleus was effective in only one case. All chemoreceptor afferent fibres had calculated conduction velocities less than 4 m/s and all were activated from the dorsomedial and medial subnuclei of the ipsilateral n.t.s. In twelve of the thirteen neurones investigated in detail there was evidence of an innervation of the commissural nucleus both at the level of the obex and behind it. In three cases this extended into the contralateral portion of the commissural nucleus. In four cases a sparse innervation of the lateral subnucleus, comprising its dorsolateral aspects, was seen. The potential significance of these distinctive patterns of projection of arterial baroreceptors and chemoreceptors is discussed in relation to cardiovascular and respiratory control.

Action Potentials↗

Synaptic mechanisms involved in the inspiratory modulation of vagal cardio-inhibitory neurones in the cat.

The respiratory modulation of the activity of vagal cardio-inhibitory neurones of the nucleus ambiguus of the cat has been investigated by electrophysiological and neuropharmacological techniques. All twenty-four vagal efferent neurones studied had axons with conduction velocities indicative of B fibres and projected to the right cardiac branches of the vagus. Their spontaneous or DL-homocysteic acid (DLH)-evoked activity showed a marked reduction during the phase of inspiration and all showed signs of receiving a baroreceptor input. Ionophoretic application of DLH always excited cardiac vagal motoneurones (c.v.m.s). Application of acetylcholine to these same cells provoked a decrease in firing rate in twelve of the fifteen neurones tested. In ten of these twelve cells simultaneous application of atropine antagonized the effect of acetylcholine. Atropine applied alone enhanced neuronal firing, particularly in inspiration. Stable intracellular recordings have been made from two c.v.m.s. These were inhibited during inspiration. Input resistance fell markedly during inspiration and injection of chloride reversed this wave of hyperpolarization to a wave of depolarization indicating that this resulted from chloride-mediated inhibitory post-synaptic potentials (i.p.s.p.s). These c.v.m.s were activated during Stage I expiration, and showed a weak and variable wave of inhibition in Stage II expiration. Pulse-rhythmic depolarizing potentials were reduced in their amplitudes during the periods of decreased neurone input resistance. It is concluded that c.v.m.s receive an excitatory input during post-inspiration and a powerful inhibitory synaptic input during inspiration. The implications of these observations for the physiology of cardiorespiratory reflexes are discussed.

Acetylcholine↗

Processing of afferent inputs in cardiovascular control.

The present report describes the use of an antidromic mapping technique to define the extent and localisation of the afferent projections of the arterial baroreceptors and chemoreceptors to the medulla oblongata. There are distinct differences in their pattern of projection: baroreceptors project primarily laterally, chemoreceptors medially, to regions which are also innervated by lung stretch afferents. Baroreceptors, however, do project to medial regions of the nucleus tractus solitarius and the significance of these patterns of projection is discussed in relation to the respiratory modifications of the performance of the baroreceptor reflex. The diencephalic control of transmission of the baroreceptor reflex is also discussed in the light of the marked innervation that the nucleus tractus solitarius receives from cell groups in the diencephalon.

Afferent Pathways↗

The location and properties of preganglionic vagal cardiomotor neurones in the rabbit.

The origins of preganglionic vagal neurons which slow the heart in the rabbit have been examined with standard neurophysiological stimulation and recording techniques. The activity of 216 neurones projecting to the right cervical vagus nerve have been recorded in localized areas of the brain stem. Thirty-six of these neurones were classified as cardiomotor neurones since they had properties similar to those described for such neurones in the cat. All had efferent axons in the range of B fibres. They could be synaptically activated by electrical stimulation of the ipsilateral aortic nerve which in the rabbit is solely barosensory. The majority of these neurones (70%) were spontaneously active and those which were normally silent could be made to fire by iontophoretic application of DL-homocysteic acid (an excitant amino acid). This spontaneous, or evoked, activity showed evidence of a pulse rhythm (of baroreceptor origin) and respiratory modulation (firing predominantly during expiration). In response to application of DL-homocysteic acid, the neuronal excitation was usually accompanied by a small but significant bradycardia. Histological examination showed that these neurones were located in both the dorsal vagal nucleus and the nucleus ambiguus.

Animals↗

Identification and brain-stem projections of aortic baroreceptor afferent neurones in nodose ganglia of cats and rabbits.

1. The retrograde transport of horseradish peroxidase (HRP) was used to locate cell bodies of afferent neurones with axons in the aortic nerves within the nodose ganglia of cats and rabbits. 2. In the rabbit HRP-labelled cells were localized to the medial aspect of the ganglion in the vicinity of the entry of the superior laryngeal and aortic nerves. 3. A similar grouping of labelled cells in rostro-medial aspects of the ganglion was seen in the cat, though there were many other labelled cells distributed throughout the ganglion. It is suggested that the former cells may be barosensory and the latter chemosensory. 4. Extracellular recordings were made from baroreceptor afferents in the nodose ganglia of rabbits and cats using glass micro-electrodes. Recordings sites were confined to rostral regions of the ganglia. 5. The projections of single baroreceptor afferents were studied by antidromic activation from the medulla oblongata using electrical stimulation applied through tungsten--glass micro-electrodes. Evidence is presented on the basis of depth--threshold contours and antidromic latency which indicates that stimulation of the main axons can be distinguished from stimulation in areas of branching and presumed termination. 6. In cats aortic baroreceptor afferents gave branches to either medial (three out of six) or lateral (three out of six) subnuclei of the nucleus tractus solitarius (n.t.s.). One neurone had additional projections to the contralateral medial subnuclei of the n.t.s. 7. In rabbits the afferents have branches mainly to lateral subnuclei of the n.t.s. (seven out of eight neurones) with only one giving branches to the medial subnucleus of the n.t.s. and additionally to the nucleus alaris. 8. Projections to the medulla extending beyond the immediate vicinity of the n.t.s. were found in either species.

Action Potentials↗

The brain-stem projections of pulmonary stretch afferent neurones in cats and rabbits.

1. Micro-electrode recordings were made from slowly adapting pulmonary stretch afferents within the nodose ganglia of cats and rabbits. Recordings sites were distributed throughout the ganglia. 2. The projections of these afferents to the medulla oblongata were studied by antidromic stimulation. 'Point' and 'Field' type depth--threshold curves were interpreted as corresponding to stimulation of the main afferent axons and its branches, respectively. Increases in antidromic latency in conjunction with 'field' contours was additional evidence in support of this interpretation. 3. In cats, most (six out of seven) afferents had extensive branches, and probably also terminations, within the medial subnucleus of the ipsilateral nucleus tractus solitarius (n.t.s.). Two of these, plus one other afferent, also had projections to the lateral and ventrolateral subnuclei. 4. In rabbits the projections of such afferents were similar, i.e. mainly to the medial subnucleus of the n.t.s. (eight out of eleven) but also extending into the nucleus alaris, and occasionally to lateral and ventrolateral subnuclei (two out of eleven) or to both regions (one out of eleven). 5. Branching of single afferents was seen to occur over up to 3 mm of the rostro-caudal extent of the intermediate region of the n.t.s. The significance of the observations is discussed.

Action Potentials↗

Respiratory modulation of afferent terminal excitability in the nucleus tractus solitarius.

The excitability of vagal and carotid sinus nerve afferent terminals within the nucleus of the tractus solitarius has been studied in cats and rabbits using the technique of antidromic activation. Although the excitability of superior laryngeal nerve afferent terminals was observed to fluctuate in phase with the central respiratory cycle, no equivalent variations in sinus nerve terminal excitability were observed. Whilst recording from single identified vagal afferents, no respiratory-related changes in the excitability of baroreceptor afferent terminals could be demonstrated, though such modifications in terminal excitability were readily seen in lung stretch afferent terminals.

Afferent Pathways↗

Effects of acetylcholine on respiratory neurones in the nucleus ambiguus-retroambigualis complex of the cat.

1. The effects of ionophoretic application of acetylcholine (ACh) and cholinergic antagonists to respiratory neurones of the nucleus ambiguus-retroambigualis complex were studied in cats. 2. Acetylcholine was ineffective when applied to inspiratory neurones (27/31) but inhibited the spontaneous activity of a significant population of expiratory neurones (21/39). 3. The expiratory neurones inhibited by ACh included neurones with axons projecting to the vagus or spinal cord, as well as neurones not antidromically activated from either of these sites. 4. The cholinergic inhibition of expiratory neurones was blocked by atropine (6/9) but dihydro-beta-erythroidine was ineffective. In seven expiratory neurones, ionophoresis of atropine alone evoked firing during the normal period of silence of the neurone (inspiration). 5. It is concluded that a significant population of expiratory neurones receive an active inhibition during inspiration and this involves a cholinergic mechanism. The implications of these observations for the synaptology of central respiratory control and modifications of the vagal outflow to the heart are discussed.

Acetylcholine↗