Biomedical subjects

K M Spyer

Publications and source records attributed to K M Spyer.

At least 73 records · Page 4Linked to original sources

PubMed1993

Essential organization of the sympathetic nervous system.

The sympathetic nervous system consists of efferent neurones supplying the viscera. The cell bodies of preganglionic neurones are located in four areas in the thoracolumbar cord; however, the majority are found in the IML. Various tracing techniques have provided information concerning the location of the cell bodies of sympathetic preganglionic neurones projecting into various nerves and ganglia and regulating the adrenal gland, the kidney and the sympathetic supply to skeletal muscle. Numerous supraspinal neurones project to the neuropil surrounding sympathetic preganglionic neurones and may form synaptic contacts with these neurones. The areas of the brain that project to the IML appear to be part of a network of reciprocally connected supraspinal cell groups. Although much emphasis has been placed on the importance of the RVLM in the mediation of tonic and phasic inputs to sympathetic preganglionic neurones, it appears that other areas are of significant import; the RVLM should not be considered to be 'the vasomotor centre'. Spinal and cranial afferents influence the sympathetic nervous system. Baroreceptor afferents terminate in the NTS and may utilize an excitatory amino acid as their neurotransmitter. However, a number of neuropeptides are also associated with these afferents. Neurones within the NTS project to a number of brain stem areas thought to be involved in the regulation of sympathetic activity; consequently the baroreceptor reflex may be mediated over a number of parallel pathways involving both supraspinal and spinal sites of inhibition. Many neurotransmitters are thought to regulate the activity of sympathetic preganglionic neurons: monoamines, peptides and amino acids. Matching the chemical content of the cell bodies of neurones within a particular cell group with physiological characteristics is a challenging task; some barosensitive neurones of the RVLM do not appear to be adrenergic although they are in the midst of the C1 adrenergic cell group. Besides acetylcholine and noradrenaline, neurotransmission in the periphery appears to involve numerous peptides and ATP.

Animals↗

PubMed1993

Hypothalamic-evoked effects in cat nucleus tractus solitarius facilitating chemoreceptor reflexes.

In anaesthetized cats intracellular recordings in the nucleus tractus solitarius (NTS) have been used to identify neurones receiving inputs from the carotid sinus nerve (SN), the aortic nerve and hypothalamic defence area (HDA). In forty-four neurones activated by SN stimulation HDA activation evoked an IPSP in fourteen (32%) and an EPSP in eight (11%). Those neurones receiving an HDA-evoked IPSP, and tested for reflex inputs, responded only to baroreceptor activation. Neurones receiving HDA-evoked EPSPs responded only to chemoreceptor activation. In three neurones unaffected by SN stimulation, short latency inputs from HDA were observed, suggesting direct monosynaptic inputs.

Action Potentials↗

PubMed1993

Physiological aspects of autonomic nervous system function.

Investigations continue into the central neuronal circuitry involved in cardiovascular control, the activity of sympathetic efferents, cardiovascular responses, and experimental hypertension. Neurons within the ventrolateral medulla are integral to several reflex pathways. The activation of neurons within the A5 cell group can generate complex patterns of sympathetic and cardiovascular response. The type of respiratory modulation of a sympathetic neuron may be associated with its function. Opioid mechanisms within the central nervous system are important in cardiovascular responses to hemorrhage. The central actions of angiotensin II and atrial natriuretic peptide may blunt the baroreceptor reflex in spontaneously hypertensive rats.

Afferent Pathways↗

PubMed1992

gamma-Aminobutyric acid immunoreactive structures in the nucleus tractus solitarius: a light and electron microscopic study.

gamma-Aminobutyric acid immunoreactive perikarya and boutons in the nucleus tractus solitarius of the cat were examined at both the light and electron microscopic level. Immunoreactive neurones were found predominantly in the parvocellular subdivision of the nucleus tractus solitarius and to a lesser degree in all the other subdivisions of the nucleus tractus solitarius and the dorsal vagal motonucleus. All the immunoreactive perikarya observed were similar in size and morphology. gamma-Aminobutyric acid immunoreactive boutons were observed throughout the nucleus tractus solitarius. However, in contrast to its high content of immunoreactive perikarya the parvocellular subdivision contained the lowest density of immunoreactive boutons. Ultrastructural examination of immunoreactive boutons in the different regions of the nucleus tractus solitarius revealed that they formed synaptic specializations, predominantly with dendritic shafts, all of which were of the symmetric type. This pattern of innervation was observed throughout the medial, commissural, ventrolateral and parvocellular subdivisions of the nucleus tractus solitarius.

Animals↗

PubMed1992

5-Hydroxytryptamine-3 receptors modulate synaptic activity in the rat nucleus tractus solitarius in vitro.

Whole-cell patch clamp recordings were made from neurons in the rat nucleus tractus solitarius (NTS) in transverse brainstem slices. 5-Hydroxytryptamine (5-HT, 100 microM) and the selective 5-HT3 receptor agonist 2-methyl-5-HT (2-CH3-5-HT, 100 microM) depolarized 86% of NTS neurons at resting membrane potential (Vm). This response was resistant to tetrodotoxin (TTX) and Co2+ application. In addition, 2-CH3-5-HT (500 nM-100 microM) increased the amplitude and frequency of both excitatory and inhibitory spontaneous synaptic potentials. This effect was also TTX-resistant, but was abolished by Co2+. The effects of 2-CH3-5-HT on EPSPs and IPSPs evoked by electrical stimulation of the tractus solitarius (TS) were analyzed separately in the presence of bicuculline or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. Concentrations of 2-CH3-5-HT between 500 nM and 1 microM decreased the amplitude of evoked EPSPs and IPSPs with similar potency. The selective 5-HT3 receptor antagonists ICS 205-930 (10 nM) and MDL 72222 (10 microM) reversibly blocked the effects of 2-CH3-5-HT at all doses examined. It is concluded that 5-HT3 receptors can mediate both pre- and postsynaptic responses in the NTS.

Animals↗

PubMed1992

The actions of baclofen on neurones and synaptic transmission in the nucleus tractus solitarii of the rat in vitro.

1. Intracellular and whole-cell patch recordings were made from sixty-seven neurones located in the nucleus tractus solitarii (NTS) in transverse slices of rat brainstem. 2. Baclofen at concentrations of 2-20 microM caused hyperpolarization from normal resting membrane potentials (Vm). This response was associated with a decrease in input resistance (Rm) tested by current pulses in discontinuous current clamp mode when membrane potential was restored to control level by current injection. In single electrode discontinuous voltage clamp mode, baclofen at these concentrations caused a small (< 50 pA) outward current associated with increased membrane conductance measured by voltage steps from holding potentials (Vh) of -50 or -60 mV. Current-voltage relations at these Vhs and the results of varying Vh between -50 and -110 mV during responses to baclofen gave a reversal potential of -73 mV. The amplitudes of baclofen responses were related to K+ concentration tested by comparing responses in media containing 1-24 mM extracellular K+, indicating that postsynaptically baclofen acts via a K+ conductance. 3. These effects were still apparent in the presence of tetrodotoxin (which did not abolish all spontaneous synaptic activity) and also in medium containing a combination of Co2+, the excitatory amino acid antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and the GABAA antagonist bicuculline which blocked synaptic activity. 4. The amplitude and frequency of spontaneous postsynaptic potentials (spPSPs) and spontaneous postsynaptic currents (spPSCs) were reduced by baclofen at concentrations (1 microM or less) which had no effect on membrane potential or holding current in current or voltage clamp recordings respectively. 5. The amplitude of evoked excitatory (evEPSPs/evEPSCs) and inhibitory (evIPSPs/evIPSCs) synaptic events elicited by electrical stimulation in the vicinity of the tractus solitarius (TS) was reduced by low concentrations of baclofen (250 nM-1 microM) which did not produce discernible postsynaptic responses. 6. In order to examine the effects of baclofen on excitatory synaptic events without contamination with inhibitory events, stimulation of the TS was carried out in the presence of bicuculline. Conversely to investigate actions on purely inhibitory synaptic responses experiments were carried out with CNQX in the bathing solution. Inhibitory synaptic responses could still be evoked, presumably by stimulation of interneurones in the vicinity of the TS. IPSPs/IPSCs were more sensitive to baclofen than EPSPs/EPSCs. 7. The effects of baclofen on membrane potential or holding current and PSP/PSCs were antagonized by 2-hydroxysaclofen (400 microM) confirming that baclofen was acting at gamma-aminobutyric acid (GABA)B receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1991

Responses of rostroventrolateral medulla spinal vasomotor neurones to chemoreceptor stimulation in rats.

The activity of spinal projecting 'vasomotor' neurones of the rostroventrolateral medulla (RVL) has been recorded in anaesthetised and paralysed rats. They responded to carotid body chemoreceptor stimulation (0.208 M NaH2PO4) with an increase in discharge that preceded an evoked increase in arterial blood pressure. This initial excitatory response was followed by a fall in discharge correlated to the rise in blood pressure. RVL neurones, which had equivalent sensitivity to baroreceptor inputs but no spinal projecting axons, failed to exhibit the initial excitatory response on chemoreceptor stimulation. These observations suggest that the pressor response to chemoreceptor stimulation is mediated, at least partially, by excitation of RVL-spinal 'vasomotor' neurones.

Animals↗

PubMed1991

Reticulospinal vasomotor neurones in decerebrate rats: effect of pentobarbitone.

The pattern of discharge of rostroventrolateral 'vasomotor' neurones has been studied in the decerebrate rat before and following the administration of pentobarbitone. Baroreflex inputs were effective in both situations, but the sensitivity of the reflex was heightened in the anaesthetised decerebrate condition even though the anaesthetic depressed neuronal discharge. The application of this anaesthetic failed to depress the inhibitory action of iontophoretically applied gamma-aminobutyric acid whose effectiveness was, if anything, enhanced. Arterial blood pressure was also reduced on the administration of the anaesthetic. These observations, taken together, suggest that the action of this, and potentially other anaesthetic agents, in lowering blood pressure may be mediated, in part, by the lowering of activity of these rostroventrolateral 'vasomotor' neurones.

Animals↗

PubMed1991

The effects of electrical stimulation of lobule IXb of the posterior cerebellar vermis on neurones within the rostral ventrolateral medulla in the anaesthetised cat.

This study was designed to investigate the effects of electrical stimulation of sublobule IXb of the posterial cerebellar vermis (the uvula) on the activity of neurones in the rostroventral medulla (RVLM) of anaesthetised cats. The ongoing activity of 38 RVLM neurones was studied in detail. One group consisted of 22 neurones that had axons projecting to the spinal cord (Group A, 22 neurones), the second had only an excitatory synaptic input from the spinal cord (Group B, 14 neurones) and the last were inhibited by equivalent spinal cord stimulation (Group C, 2 neurones). In Group A 16 neurones were excited, 2 inhibited and the other 5 showed a biphasic response involving excitation followed by inhibition, to lobule IXb stimulation. In Group B, lobule IXb stimulation excited 9 cells, inhibited 2 and evoked a biphasic response in 3 neurones. In Group C both cells were inhibited on cerebellar stimulation. Some cells in Group A and B were affected by electrical stimulation of the carotid sinus nerve--the predominant effect being an excitation. Specific baroreceptor stimulation invariably caused inhibition and several neurones had pulse modulated discharge. These data indicate that stimulation of sublobule IXb has marked influences on RVLM neuronal activity including a proportion of those neurones that have axons descending to the spinal cord that has been described as presympathetic 'vasomotor' neurones. A striking finding is the more widespread action of sublobule IXb, baroreceptor and sinus nerve inputs on other neurones of the RVLM, and the implications of this for the integration of cardiovascular control are discussed.

Anesthesia↗

PubMed1991

The influence of lobule IX of the cerebellar posterior vermis on the baroreceptor reflex in the decerebrate rabbit.

Stimulation of lobule IX (the uvula) of the cerebellar posterior vermis, either electrically or chemically, has been shown to evoke marked cardiovascular effects in both rabbit and cat. Recent experiments suggest that this stimulation can also reduce the responsiveness of neurons in the nucleus tractus solitarii to baroreceptor inputs. The aim of the present study was thus to determine whether the uvula exerts an influence on the baroreceptor reflex. In order to evoke a reflex bradycardia in decerebrate rabbits, blood pressure was increased by inflating a Swan-Ganz catheter positioned in the descending aorta, and in some rabbits the aortic nerve was also stimulated electrically. In most rabbits, following uvula removal, significantly larger reflex falls in heart rate were observed. In a second group of rabbits, a lesion of cerebellar lobules VI-VIII had no effect on reflex bradycardia. It is concluded that the uvula tonically depresses the cardioinhibitory component of the baroreceptor reflex in the rabbit. The possible functional implications of these results are discussed.

Animals↗

PubMed1991

The role of the posterior cerebellar vermis in cardiovascular control.

The effects of electrical stimulation of the posterior cerebellar vermis in anaesthetized, decerebrate and conscious animals are described, and include marked changes in blood pressure and heart rate and an inhibition of the baroreceptor reflex. These effects appear to be restricted to lobule IX, and can be duplicated by chemical stimulation, indicating that they are a genuine cerebellar phenomenon. The results of both neuroanatomical and neurophysiological experiments to investigate the pathways responsible for the effects are described, and these show there to be a direct projection of Purkinje cell axons to the parabrachial nucleus. Experiments designed to test a possible involvement of lobule IX in the alerting response have proved negative, and while lobule IX itself appears to have no role in conditioned cardiovascular responses, lesions of lobules VI and VII do result in a significant impairment of the acquisition of conditioned bradycardia in the rabbit.

Animals↗

PubMed1991

Localization of [125I]endothelin binding sites in the region of the carotid bifurcation and brainstem of the cat: possible baro- and chemoreceptor involvement.

We have demonstrated by autoradiography, displaceable binding for [125I]endothelin-1 ([125I]ET-1), [125I]endothelin-2 ([125I]ET-2), and [125I]endothelin-3 ([125I]ET-3) in the cat carotid bifurcation as well as in the nucleus of the tractus solitarius, where baroreceptor and chemoreceptor afferents from the carotid body and sinus terminate. There was also significant binding in the nodose and superior cervical ganglia. Barosensory and chemosensory discharge was recorded from filaments of the carotid sinus nerve in cats anesthetized with pentobarbitone. Intra-carotid injection of ET-1 or ET-3 (4-402 pmoles) caused transient dose-related depression of baroreceptor discharge without any immediate effects on systemic blood pressure (BP) or heart rate; there was a delayed biphasic effect on BP. ET-1 had little effect on chemosensory discharge during the first 15 s post-injection, but there was a delayed (45-90 s) dose-related increase in discharge. The effects of all three ETs were qualitatively similar, and ET enhanced chemoexcitation evoked by either acetylcholine or sodium cyanide. Our results show that (a) ET binding sites are located in the baroreceptor and chemoreceptor afferent pathways and (b) ETs can influence afferent activity of baroreceptors and chemoreceptors. Further studies are needed to determine the significance of these findings, particularly with regard to reflex control of the cardiovascular system.

Animals↗

PubMed1991

GABA-mediated inhibition of medullary vasomotor neurones by area postrema stimulation in rats.

1. The cardiovascular responses, together with the effects on medullary sympathoexcitatory (vasomotor) neurones of the rostral ventrolateral medulla, of area postrema stimulation have been studied in vivo. 2. Electrical (10 Hz) or chemical stimulation using microinjections of L-glutamate of the area postrema produced a vasodepressor response and an inhibition of the medullary sympathoexcitatory neurones in the nucleus reticularis rostroventrolateralis (RVL), while similar stimulation in the adjacent nucleus tractus solitarii (NTS) caused increases in arterial pressure. 3. Single-pulse stimulation of the area postrema revealed at least three influences on the activity of RVL vasomotor neurones, one being excitatory and two inhibitory. 4. The inhibitions evoked in the medullary vasomotor neurones on area postrema stimulation were blocked by ionophoretic application of bicuculline, a GABAA receptor antagonist, without altering the excitatory input to the same neurones. Bilateral microinjections of bicuculline into the RVL in regions where the vasomotor neurones had been identified totally eliminated the vasodepression due to area postrema stimulation. 5. These data support a role for the area postrema in cardiovascular control. It is concluded that the area postrema exerts its action on cardiovascular control in part via GABAergic inhibition of the 'vasomotor' neurones in the nucleus reticularis rostroventrolateralis.

Action Potentials↗

PubMed1991

Nociceptive inputs into rostral ventrolateral medulla-spinal vasomotor neurones in rats.

1. In anaesthetized rats recordings were made from thirty-eight neurones in the rostral ventrolateral medulla (RVL) with spinal-projecting axons. Their responses to mechanical, thermal and/or electrical stimulation were examined as were the accompanying changes in arterial pressure. 2. Mechanical, thermal and electrical stimulation of either hindpaw at a strength that can be regarded as noxious produced a consistent rise in arterial pressure. RVL-spinal-projecting 'vasomotor' neurones were excited by the noxious mechanical and thermal (52 degrees C) stimulation at a latency that was shorter than that of the evoked pressor response. 3. Percutaneous electrical stimulation of either hindlimb extremity resulted in an early peak of excitation (fourteen out of fourteen), an early trough of inhibition (twelve out fourteen), and a later peak of excitation (two out of fourteen). This response pattern to stimulation of either limb was independent of which limb was activated, but contralateral hindpaw stimulation elicited excitation at a shorter latency. The differences in latency of responses to stimulating two locations along the tail suggested that the early excitation and inhibition of RVL-spinal 'vasomotor' neurones were evoked by activation of peripheral fibres with a mean conduction velocity in the A delta range. 4. Short-latency excitatory and inhibitory responses in RVL-spinal 'vasomotor' neurones were observed also when single-pulse stimuli were delivered within the lateral part of the spinal cord. 5. Ionophoretic application of bicuculline, a GABAA receptor antagonist, blocked the evoked inhibition of these neurones on electrical stimulation of the hindpaw without attenuating the excitatory input from the same stimulus. 6. These results indicate that RVL-spinal 'vasomotor' neurones receive an input from cutaneous nociceptive afferents. This suggests that these neurones mediate, at least partly, the cardiovascular responses related to nociceptor stimulation.

Animals↗

PubMed1990

An electrophysiological and anatomical study of afferents reaching the cerebellar uvula in the rabbit.

Stimulation of a medial region of the cerebellar uvula cortex produces sympathetically mediated cardiovascular effects in the decerebrate rabbit. In the present study the afferents to this cerebellar area have been determined using electrophysiological and neuroanatomical methods. Field potentials of prevalent mossy origin evoked by single-shock stimulation of different peripheral nerves have been recorded from sublobules IXa and IXb. No response to vagus and aortic nerves stimulation has been found. A modulation of Purkinje cell discharge following natural vestibular stimulation has been found. A modulation of Purkinje cell discharge following natural vestibular stimulation has been recorded from sublobules IXb and IXc. The retrograde transport of horseradish peroxidase from the uvula cortex has revealed a widespread afferent input to this cerebellar region arising from brain stem reticular and sensory nuclei. On the basis of the results obtained, together with the results of experiments performed in conscious rabbits, contained in the following paper (Bradley, Ghelarducci, La Noce & Spyer, 1990), it is suggested that the uvula participates in co-ordination of the visceral and somatic components of the alerting reaction in the rabbit.

Afferent Pathways↗

PubMed1990

Autonomic and somatic responses evoked by stimulation of the cerebellar uvula in the conscious rabbit.

The present study has investigated the effects of electrical stimulation of the cerebellar posterior cortex in the conscious rabbit. Stimulation of lobule IX (the uvula) elicited an increase in mean arterial blood pressure and heart rate, accompanied by EEG desynchronization, pupillary dilatation and a specific motor reaction, consisting of pricking of the ears, neck stiffening and running movements. Stimulation of lobule VIII was ineffective in evoking equivalent responses. The administration of barbiturates reversed the cardiovascular response to uvula stimulation, producing a fall in mean arterial pressure. The characteristics of the pattern of responses obtained, together with the anatomical and electrophysical observations provided in the preceding paper (Bradley, Ghelarducci, La Noce, Paton, Spyer & Withington-Wray, 1990), suggest a possible involvement of uvula cortex in the expression of the alerting reaction in the rabbit.

Analysis of Variance↗

PubMed1990

Brain stem regions mediating the cardiovascular responses elicited from the posterior cerebellar cortex in the rabbit.

1. In this study we have examined the roles of the lateral parabrachial nucleus (lateral PBN) and nucleus tractus solitarius (NTS) as sites mediating the circulatory responses evoked from lobule IX b of the posterior cerebellar vermis in the decerebrate and anaesthetized decerebrate rabbit. Microinjection of either kainic acid or bicuculline into the lateral PBN and NTS was undertaken to assess the importance of neurones and GABAergic mechanisms, respectively, in expressing the cardiovascular responses evoked from lobule IX b. 2. In both the decerebrate and anaesthetized decerebrate rabbit activation of neurones within the lateral PBN with a microinjection of glutamate elicited tachycardia and a pressor response together with an increase in renal sympathetic nerve discharge and vasoconstriction in the hindlimb. A microinjection of GABA into the lateral PBN evoked an opposite pattern of response. Chemical lesioning of neurones within the rostral region of the lateral PBN or pharmacological blockade of GABAA receptor, abolished or significantly attenuated the cardiovascular response (bradycardia/depressor effect) evoked from lobule IX b in the anaesthetized decerebrate rabbit. 3. In the decerebrate animal the tachycardia/pressor response elicited from lobule IX b was suppressed when either kainic acid or bicuculline was microinjected into the caudal division of the lateral PBN. 4. A bradycardia, depressor response, an abolition of on-going renal nerve activity and vasodilatation in the femoral bed were evoked by activating neurones within a restricted region of the NTS with glutamate in the decerebrate and anaesthetized decerebrate rabbit. A microinjection of GABA into the NTS produced a qualitatively opposite pattern of response. The bradycardia/depressor response evoked from lobule IX b in the anaesthetized decerebrate rabbit was not altered significantly following a microinjection of either kainic acid or bicuculline into the ipsilateral NTS. However, in the decerebrate preparation following a microinjection of bicuculline into the ipsilateral NTS the tachycardia/pressor response evoked from IX b was either abolished or in many cases reversed to the pattern of response seen in the anaesthetized decerebrate rabbit. 5. The present experiments provide evidence for two functionally distinct pathways from the cardiovascular region of lobule IX b to the lateral PBN.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Inhibition of barosensitive neurones evoked by lobule IXb of the posterior cerebellar cortex in the decerebrate rabbit.

1. Electrical stimulation of lobule IXb of the posterior cerebellar vermis evoked an increase in heart rate and arterial pressure in the decerebrate rabbit. This pattern of response was followed by a rebound bradycardia which was maintained until arterial pressure had returned to control levels. Activation of the arterial baroreceptors during IXb stimulation failed to elicit reflex changes in heart rate and arterial blood pressure. 2. Extracellular recordings were made from eighty-one single neurones in the nucleus tractus solitarius (NTS), and adjacent structures, that received inputs from the carotid sinus nerve, aortic nerve and/or vagus. A proportion of these were characterized as baro- or chemosensitive by physiological stimuli. The nature of the input from lobule IXb onto these cells was studied subsequently. 3. In twenty-seven out of thirty-five barosensitive neurones, stimulation of lobule IXb either decreased or abolished on-going activity. The latency to onset of inhibition was 21 ms in fourteen cells. In a further twenty-one neurones the spikes evoked orthodromically by electrical stimulation of either the aortic or sinus nerves were either inhibited or severely reduced in number during short-train conditioning stimulation of lobule IXb. This effect was most potent when the cortical conditioning stimulus was timed to occur 25 ms before the aortic or carotid sinus nerves were stimulated. 4. It is suggested that stimulation of lobule IXb in the decerebrate rabbit expresses its influence on the cardiovascular system in part by an inhibitory action on neurones receiving baroreceptor inputs at the level of the NTS.

Animals↗