K. Spyer - Academia.edu (original) (raw)
Papers by K. Spyer
The tachypnoea evoked by non-peptidic delta opiate receptor agonists, but not that due to chest c... more The tachypnoea evoked by non-peptidic delta opiate receptor agonists, but not that due to chest compression, is blocked by Naltrindole in the anaesthetised rabbit T.A. Sears1 and D. Banks2 1Department of Physiology, GKT, King’s College London, London, UK and 2Department of Biological Sciences, The Open University, Milton Keynes, UK Non-peptidic δ-opioid receptor agonists offer the prospect of analgesia free fromtherespiratorydepressionduetoμ-receptoragonists (as with oral SB 235863 in the rat,Pozzi et al. 1998).Given to anaesthetised rabbits I.V., SB 235863 actually evoked a tachypnoea abolished by cervical vagotomy (Sears & Banks,2002) as now described for twootherδagonists.NewZealandwhiterabbits (2.0-3.0kg)were anaesthetised with Na pentobarbitone (40-60 mg/kg I.P.) and subsequently by constant I.V. infusion (6-8 mg/kg/h). Carotid BP was measuredandearand jugularveinscannulated forgiving fluidsand drugs. Silver ball electrodes sealed 3.0 mm apart on a plastic strip recorded the EM...
Journal of the Autonomic Nervous System, 1995
Extracellular recordings were made from 46 sympathetic preganglionic neurones (SPNs) in a neonata... more Extracellular recordings were made from 46 sympathetic preganglionic neurones (SPNs) in a neonatal rat brainstem-spinal cord preparation. Neurones were identified as SPNs as they were: (i) activated at constant latencies (2-10 ms) following stimulation of the ventral root, which indicated antidromic activation and (ii) recorded at sites located either in the intermediolateral cell column or the intercalated nucleus of the thoracic spinal cord. Over one-third of the neurones (n = 17) recorded displayed ongoing activity with firing frequencies of 0.3-5 Hz. Of the neurones analyzed only one showed a very obvious phasic firing pattern. Dorsal root stimulation evoked firing in 16 of 26 SPNs recorded from the same spinal segment (6 of 10 with ongoing activity). The types of responses observed varied between neurones. The excitation of all neurones was characterised by a response occurring at a latency of 6-50 ms. In addition, SPNs in 'spinalised' preparations (n = 2) responded with latencies of 10-40 ms, similar to those observed in the intact preparation. The latencies of responses in SPNs were longer and more variable than those observed in ventral horn motor neurones. This indicates that a spinal polysynaptic pathway was involved in mediating these responses. In 7 SPNs dorsal root stimulation also elicited longer latency responses which were observed up to 1000 ms after stimulation. These responses may involve activation of bulbospinal and/or propriospinal pathways. These results show that the neonatal rat brainstem-spinal cord preparation is viable for studying SPNs and that dorsal root-SPN reflexes are intact.
1990 IJCNN International Joint Conference on Neural Networks, 1990
This research is based on the premise that computational principles evolved by biological systems... more This research is based on the premise that computational principles evolved by biological systems are applicable to engineering devices, that an interaction of ongoing neurobiological experiments with computer simulation will be productive in extracting computational principles, and that tools for the analysis of neurobiological systems and for their modeling and simulation have evolved to the point where success is probable. The approach is based on neuroanatomical experiments to establish the connectional circuit. However, it is found that knowledge of network architecture (connectivity) is not enough. The biophysics of neurons leads to important diversity of intrinsic properties among constituents of a network. Consequently, neurons have dynamical response properties that can sensitively affect, or even completely alter, the functioning of a distributed network. Experimentally determined facts of both connection and biophysics must inform computational models in order to capture network dynamics/performance. Simulation results in turn generate hypotheses which drive further testing in biological experiments
Cardiovascular Research, 2012
Innate mechanisms of inter-organ protection underlie the phenomenon of remote ischaemic precondit... more Innate mechanisms of inter-organ protection underlie the phenomenon of remote ischaemic preconditioning (RPc) in which episode(s) of ischaemia and reperfusion in tissues remote from the heart reduce myocardial ischaemia/reperfusion injury. The uncertainty surrounding the mechanism(s) underlying RPc centres on whether humoral factor(s) produced during ischaemia/reperfusion of remote tissue and released into the systemic circulation mediate RPc, or whether a neural signal is required. While these two hypotheses may not be incompatible, one approach to clarify the potential role of a neural pathway requires targeted disruption or activation of discrete central nervous substrate(s). Methods and results Using a rat model of myocardial ischaemia/reperfusion injury in combination with viral gene transfer, pharmaco-, and optogenetics, we tested the hypothesis that RPc cardioprotection depends on the activity of vagal pre-ganglionic neurones and consequently an intact parasympathetic drive. For cell-specific silencing or activation, neurones of the brainstem dorsal motor nucleus of the vagus nerve (DVMN) were targeted using viral vectors to express a Drosophila allatostatin receptor (AlstR) or light-sensitive fast channelrhodopsin variant (ChIEF), respectively. RPc cardioprotection, elicited by ischaemia/reperfusion of the limbs, was abolished when DVMN neurones transduced to express AlstR were silenced by selective ligand allatostatin or in conditions of systemic muscarinic receptor blockade with atropine. In the absence of remote ischaemia/reperfusion, optogenetic activation of DVMN neurones transduced to express ChIEF reduced infarct size, mimicking the effect of RPc. Conclusion These data indicate a crucial dependence of RPc cardioprotection against ischaemia/reperfusion injury upon the activity of a distinct population of vagal pre-ganglionic neurones.
Journal of Physiology-london, 2010
Arterial P CO 2 , a major determinant of breathing, is detected by chemosensors located in the br... more Arterial P CO 2 , a major determinant of breathing, is detected by chemosensors located in the brainstem. These are important for maintaining physiological levels of P CO 2 in the blood and brain, yet the mechanisms by which the brain senses CO 2 remain controversial. As ATP release at the ventral surface of the brainstem has been causally linked to the adaptive changes in ventilation in response to hypercapnia, we have studied the mechanisms of CO 2-dependent ATP release in slices containing the ventral surface of the medulla oblongata. We found that CO 2-dependent ATP release occurs in the absence of extracellular acidification and correlates directly with the level of P CO 2. ATP release is independent of extracellular Ca 2+ and may occur via the opening of a gap junction hemichannel. As agents that act on connexin channels block this release, but compounds selective for pannexin-1 have no effect, we conclude that a connexin hemichannel is involved in CO 2-dependent ATP release. We have used molecular, genetic and immunocytochemical techniques to demonstrate that in the medulla oblongata connexin 26 (Cx26) is preferentially expressed near the ventral surface. The leptomeninges, subpial astrocytes and astrocytes ensheathing penetrating blood vessels at the ventral surface of the medulla can be loaded with dye in a CO 2-dependent manner, suggesting that gating of a hemichannel is involved in ATP release. This distribution of CO 2-dependent dye loading closely mirrors that of Cx26 expression and colocalizes to glial fibrillary acidic protein (GFAP)-positive cells. In vivo, blockers with selectivity for Cx26 reduce hypercapnia-evoked ATP release and the consequent adaptive enhancement of breathing. We therefore propose that Cx26-mediated release of ATP in response to changes in P CO 2 is an important mechanism contributing to central respiratory chemosensitivity.
Brain Res Bull, 2000
Evidence is provided that purine nucleotides play a major role in modulating cardio-respiratory c... more Evidence is provided that purine nucleotides play a major role in modulating cardio-respiratory control through actions at specific sites in the central nervous system (CNS). The accumulation of adenosine in the extracellular space of the nucleus tractus solitarius (NTS) on hypothalamic defence area stimulation is described, and is shown to result from the extracellular breakdown of neurally released adenosine triphosphate (ATP). The actions of adenosine in modulating synaptic actions in the NTS are discussed in relation to the potential presynaptic action of adenosine in modulating transmitter release. Actions of adenosine and ATP at other sites in the medulla concerned with cardio-respiratory control are discussed. The interrelationships between ATP and adenosine are mentioned.
Experimental physiology, 1993
In anaesthetized cats intracellular recordings in the nucleus tractus solitarius (NTS) have been ... more 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.
The Journal of physiology, 1973
Journal of neurophysiology, 1974
ABSTRACT
Journal of the autonomic nervous system, 1989
Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute to the regulati... more Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute to the regulation of arterial baroreceptor-vagal reflex sensitivity. To obtain additional data relevant to this suggestion, interactions between stimulation of the ACE and arterial baroreceptor afferent activation were examined. New Zealand rabbits were anesthetized with alpha-chloralose and a stimulating electrode was implanted stereotaxically in the ACE. In the first series of experiments, cardiovascular responses to stimulation of the ACE were assessed during periods in which blood pressure was decreased using sodium nitroprusside or increased in the rostral arterial compartment by inflating the tip of a Swan-Ganz catheter positioned in the descending aorta. It was found that the magnitude of bradycardia to stimulation of the ACE was correlated with the level of arterial blood pressure at the onset of stimulation, such that higher blood pressures were associated with larger bradycardic responses. Th...
The Journal of physiology, 1977
Advances in experimental medicine and biology, 2004
ABSTRACT Respiratory drive is sensitive to small changes in arterial PO2 and PCO2 which are sense... more ABSTRACT Respiratory drive is sensitive to small changes in arterial PO2 and PCO2 which are sensed by the peripheral chemoreceptors located within the carotid and aortic bodies and by central chemoreceptors localised within the brain (Gonzalez et al., 1994; Daly, 1997; Nattie, 1999; Prabhakar, 2000). In adult mammals type I (glomus) cells of the carotid body are the primary peripheral chemosensitive elements which detect changes in arterial PO2 (Gonzalez et al., 1994; Prabhakar, 2000) and transmit this information to the afferent nerve fibres of the carotid sinus nerve, which in turn relays to the brainstem respiratory centres to produce adaptive changes in ventilation. Levels of PCO2 are monitored predominantly by the central chemoreceptors localised within the medulla oblongata (primarily at, or in close proximity to, the ventral medullary surface [Loeschcke, 1982]), as up to 80% of the CO2-evoked ventilatory response is mediated by the action of CO2 at the brainstem chemosensitive sites (Heeringa et al., 1979).
Neuroscience and behavioral physiology, 2003
The aim of the present work was to identify the role of ATP acting on specific P2X receptors in t... more The aim of the present work was to identify the role of ATP acting on specific P2X receptors in the central mechanisms of thermoregulation. Immunohistochemical studies demonstrated that brainstem structures involved in controlling body temperature contained large number of nerve cells bearing P2X ATP receptors. Experiments on conscious rats involving intracerebroventricular administration of an ATP analog and P2X antagonists showed that both activation and blockade of central P2X receptors produced marked changes in body temperature. Analysis of the effects of these substances provided grounds for suggesting that ATP acting on P2X receptors fulfils an important function in the mechanisms of transmitting afferent information from peripheral thermal receptors to thermoregulatory centers in the brainstem with responsibility for heat loss, while in pyrogen-induced fever ATP acting on these receptors may be involved in the activity of the endogenous antipyretic system.
Neuroscience, 2001
The ventrolateral medulla has a critical role in the generation and patterning of respiration via... more The ventrolateral medulla has a critical role in the generation and patterning of respiration via an extensive network of respiratory neurones. We have investigated the effects of activating purinergic P2 receptors within the ventrolateral medulla of the anaesthetised rat on the overall pattern of respiratory activity. In addition, using immunohistochemical techniques, we have identified the subtypes of P2X receptors in the ventrolateral medulla. Unilateral microinjection of ATP into the ventrolateral medulla reduced in a dose-dependent manner, or abolished, resting phrenic nerve discharge recorded as an indication of central inspiratory drive. ATP also elicited increases in blood pressure and variable changes in heart rate. These effects were mimicked by microinjection of the P2X receptor agonist alpha,beta-methylene ATP into the ventrolateral medulla. Whilst microinjection of suramin, a P2 receptor antagonist, had no effect on resting cardiorespiratory variables it blocked the res...
The Journal of physiology, Jan 15, 1995
1. This investigation was initiated because activation of laryngeal afferents, either by electric... more 1. This investigation was initiated because activation of laryngeal afferents, either by electrical stimulation of the superior laryngeal nerve (SLN) or by natural stimulation of receptors in the laryngeal mucosa, results in a cardiorespiratory response comprising bradycardia, hypotension and apnoea (phrenic nerve activity was suppressed). This pattern of response is qualitatively equivalent to the response that is evoked on activation of the arterial baroreceptors. 2. Preliminary studies indicated that the effects of activating the SLN were suppressed during stimulation in the hypothalamic defence area (HDA) at points that also blocked the effects of baroreceptor stimulation. 3. Recordings were taken from seventy-two neurones localized within the ipsilateral nucleus tractus solitarii (NTS) whose activity was modified by SLN stimulation. Sixty neurones responded with an EPSP on SLN stimulation; nine of these had an inspiratory firing pattern. Five neurones were seen to receive an IP...
The Journal of physiology, Jan 15, 1995
1. In anaesthetized, paralysed and artificially ventilated cats, recordings have been made in the... more 1. In anaesthetized, paralysed and artificially ventilated cats, recordings have been made in the nucleus tractus solitarii (NTS) to assess further the role of this nucleus in mediating the cardiorespiratory responses that are elicited on stimulation within the hypothalamic defence area (HDA). 2. The responses of NTS neurones to stimulation in the hypothalamus were assessed, as were their patterns of evoked response to electrical stimulation of the sinus (SN), aortic (AN), superior laryngeal (SLN) and vagus (VN) nerves. 3. Stimulation in the HDA affected the activity of 110 NTS neurones (85 studied in intracellular and 25 studied in extracellular recordings). The present study focused on those sixty-eight neurones that were excited by such stimulation (51 intracellular recordings and 17 extracellular recordings). 4. Of the sixty-eight neurones that were excited by HDA stimulation, seven revealed no changes in membrane potential or evoked discharge (2 neurones) but the stimulus facil...
The Journal of physiology, 1994
1. In order to assess the importance of the parabrachial nuclei in modulating cardiorespiratory a... more 1. In order to assess the importance of the parabrachial nuclei in modulating cardiorespiratory activity, electric current or microinjections of glutamate were used to stimulate discrete regions of the parabrachial nuclei in anaesthetized rats. 2. Stimulation of cell bodies in the medial region of the parabrachial nuclei and in the Kölliker-Fuse nuclei, caused an expiratory facilitatory response. This consisted mainly of a decrease in respiratory rate as measured by observing phrenic nerve activity. 3. Stimulation of cell bodies in the lateral region of the parabrachial nuclei caused an inspiratory facilitatory response. This consisted mainly of an increase in respiratory rate. 4. At the majority of sites (16 out of 20) where changes in respiratory rate were elicited by glutamate injection or electrical stimulation an increase in blood pressure was observed. The coexistence of increases in blood pressure and heart rate indicates the presence of inhibition of the heart rate component...
Journal of the autonomic nervous system, 1981
The excitability of vagal and carotid sinus nerve afferent terminals within the nucleus of the tr... more 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.
The Journal of experimental biology, 1982
Archives italiennes de biologie, 1974
The tachypnoea evoked by non-peptidic delta opiate receptor agonists, but not that due to chest c... more The tachypnoea evoked by non-peptidic delta opiate receptor agonists, but not that due to chest compression, is blocked by Naltrindole in the anaesthetised rabbit T.A. Sears1 and D. Banks2 1Department of Physiology, GKT, King’s College London, London, UK and 2Department of Biological Sciences, The Open University, Milton Keynes, UK Non-peptidic δ-opioid receptor agonists offer the prospect of analgesia free fromtherespiratorydepressionduetoμ-receptoragonists (as with oral SB 235863 in the rat,Pozzi et al. 1998).Given to anaesthetised rabbits I.V., SB 235863 actually evoked a tachypnoea abolished by cervical vagotomy (Sears & Banks,2002) as now described for twootherδagonists.NewZealandwhiterabbits (2.0-3.0kg)were anaesthetised with Na pentobarbitone (40-60 mg/kg I.P.) and subsequently by constant I.V. infusion (6-8 mg/kg/h). Carotid BP was measuredandearand jugularveinscannulated forgiving fluidsand drugs. Silver ball electrodes sealed 3.0 mm apart on a plastic strip recorded the EM...
Journal of the Autonomic Nervous System, 1995
Extracellular recordings were made from 46 sympathetic preganglionic neurones (SPNs) in a neonata... more Extracellular recordings were made from 46 sympathetic preganglionic neurones (SPNs) in a neonatal rat brainstem-spinal cord preparation. Neurones were identified as SPNs as they were: (i) activated at constant latencies (2-10 ms) following stimulation of the ventral root, which indicated antidromic activation and (ii) recorded at sites located either in the intermediolateral cell column or the intercalated nucleus of the thoracic spinal cord. Over one-third of the neurones (n = 17) recorded displayed ongoing activity with firing frequencies of 0.3-5 Hz. Of the neurones analyzed only one showed a very obvious phasic firing pattern. Dorsal root stimulation evoked firing in 16 of 26 SPNs recorded from the same spinal segment (6 of 10 with ongoing activity). The types of responses observed varied between neurones. The excitation of all neurones was characterised by a response occurring at a latency of 6-50 ms. In addition, SPNs in 'spinalised' preparations (n = 2) responded with latencies of 10-40 ms, similar to those observed in the intact preparation. The latencies of responses in SPNs were longer and more variable than those observed in ventral horn motor neurones. This indicates that a spinal polysynaptic pathway was involved in mediating these responses. In 7 SPNs dorsal root stimulation also elicited longer latency responses which were observed up to 1000 ms after stimulation. These responses may involve activation of bulbospinal and/or propriospinal pathways. These results show that the neonatal rat brainstem-spinal cord preparation is viable for studying SPNs and that dorsal root-SPN reflexes are intact.
1990 IJCNN International Joint Conference on Neural Networks, 1990
This research is based on the premise that computational principles evolved by biological systems... more This research is based on the premise that computational principles evolved by biological systems are applicable to engineering devices, that an interaction of ongoing neurobiological experiments with computer simulation will be productive in extracting computational principles, and that tools for the analysis of neurobiological systems and for their modeling and simulation have evolved to the point where success is probable. The approach is based on neuroanatomical experiments to establish the connectional circuit. However, it is found that knowledge of network architecture (connectivity) is not enough. The biophysics of neurons leads to important diversity of intrinsic properties among constituents of a network. Consequently, neurons have dynamical response properties that can sensitively affect, or even completely alter, the functioning of a distributed network. Experimentally determined facts of both connection and biophysics must inform computational models in order to capture network dynamics/performance. Simulation results in turn generate hypotheses which drive further testing in biological experiments
Cardiovascular Research, 2012
Innate mechanisms of inter-organ protection underlie the phenomenon of remote ischaemic precondit... more Innate mechanisms of inter-organ protection underlie the phenomenon of remote ischaemic preconditioning (RPc) in which episode(s) of ischaemia and reperfusion in tissues remote from the heart reduce myocardial ischaemia/reperfusion injury. The uncertainty surrounding the mechanism(s) underlying RPc centres on whether humoral factor(s) produced during ischaemia/reperfusion of remote tissue and released into the systemic circulation mediate RPc, or whether a neural signal is required. While these two hypotheses may not be incompatible, one approach to clarify the potential role of a neural pathway requires targeted disruption or activation of discrete central nervous substrate(s). Methods and results Using a rat model of myocardial ischaemia/reperfusion injury in combination with viral gene transfer, pharmaco-, and optogenetics, we tested the hypothesis that RPc cardioprotection depends on the activity of vagal pre-ganglionic neurones and consequently an intact parasympathetic drive. For cell-specific silencing or activation, neurones of the brainstem dorsal motor nucleus of the vagus nerve (DVMN) were targeted using viral vectors to express a Drosophila allatostatin receptor (AlstR) or light-sensitive fast channelrhodopsin variant (ChIEF), respectively. RPc cardioprotection, elicited by ischaemia/reperfusion of the limbs, was abolished when DVMN neurones transduced to express AlstR were silenced by selective ligand allatostatin or in conditions of systemic muscarinic receptor blockade with atropine. In the absence of remote ischaemia/reperfusion, optogenetic activation of DVMN neurones transduced to express ChIEF reduced infarct size, mimicking the effect of RPc. Conclusion These data indicate a crucial dependence of RPc cardioprotection against ischaemia/reperfusion injury upon the activity of a distinct population of vagal pre-ganglionic neurones.
Journal of Physiology-london, 2010
Arterial P CO 2 , a major determinant of breathing, is detected by chemosensors located in the br... more Arterial P CO 2 , a major determinant of breathing, is detected by chemosensors located in the brainstem. These are important for maintaining physiological levels of P CO 2 in the blood and brain, yet the mechanisms by which the brain senses CO 2 remain controversial. As ATP release at the ventral surface of the brainstem has been causally linked to the adaptive changes in ventilation in response to hypercapnia, we have studied the mechanisms of CO 2-dependent ATP release in slices containing the ventral surface of the medulla oblongata. We found that CO 2-dependent ATP release occurs in the absence of extracellular acidification and correlates directly with the level of P CO 2. ATP release is independent of extracellular Ca 2+ and may occur via the opening of a gap junction hemichannel. As agents that act on connexin channels block this release, but compounds selective for pannexin-1 have no effect, we conclude that a connexin hemichannel is involved in CO 2-dependent ATP release. We have used molecular, genetic and immunocytochemical techniques to demonstrate that in the medulla oblongata connexin 26 (Cx26) is preferentially expressed near the ventral surface. The leptomeninges, subpial astrocytes and astrocytes ensheathing penetrating blood vessels at the ventral surface of the medulla can be loaded with dye in a CO 2-dependent manner, suggesting that gating of a hemichannel is involved in ATP release. This distribution of CO 2-dependent dye loading closely mirrors that of Cx26 expression and colocalizes to glial fibrillary acidic protein (GFAP)-positive cells. In vivo, blockers with selectivity for Cx26 reduce hypercapnia-evoked ATP release and the consequent adaptive enhancement of breathing. We therefore propose that Cx26-mediated release of ATP in response to changes in P CO 2 is an important mechanism contributing to central respiratory chemosensitivity.
Brain Res Bull, 2000
Evidence is provided that purine nucleotides play a major role in modulating cardio-respiratory c... more Evidence is provided that purine nucleotides play a major role in modulating cardio-respiratory control through actions at specific sites in the central nervous system (CNS). The accumulation of adenosine in the extracellular space of the nucleus tractus solitarius (NTS) on hypothalamic defence area stimulation is described, and is shown to result from the extracellular breakdown of neurally released adenosine triphosphate (ATP). The actions of adenosine in modulating synaptic actions in the NTS are discussed in relation to the potential presynaptic action of adenosine in modulating transmitter release. Actions of adenosine and ATP at other sites in the medulla concerned with cardio-respiratory control are discussed. The interrelationships between ATP and adenosine are mentioned.
Experimental physiology, 1993
In anaesthetized cats intracellular recordings in the nucleus tractus solitarius (NTS) have been ... more 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.
The Journal of physiology, 1973
Journal of neurophysiology, 1974
ABSTRACT
Journal of the autonomic nervous system, 1989
Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute to the regulati... more Recent evidence suggests that the amygdaloid central nucleus (ACE) may contribute to the regulation of arterial baroreceptor-vagal reflex sensitivity. To obtain additional data relevant to this suggestion, interactions between stimulation of the ACE and arterial baroreceptor afferent activation were examined. New Zealand rabbits were anesthetized with alpha-chloralose and a stimulating electrode was implanted stereotaxically in the ACE. In the first series of experiments, cardiovascular responses to stimulation of the ACE were assessed during periods in which blood pressure was decreased using sodium nitroprusside or increased in the rostral arterial compartment by inflating the tip of a Swan-Ganz catheter positioned in the descending aorta. It was found that the magnitude of bradycardia to stimulation of the ACE was correlated with the level of arterial blood pressure at the onset of stimulation, such that higher blood pressures were associated with larger bradycardic responses. Th...
The Journal of physiology, 1977
Advances in experimental medicine and biology, 2004
ABSTRACT Respiratory drive is sensitive to small changes in arterial PO2 and PCO2 which are sense... more ABSTRACT Respiratory drive is sensitive to small changes in arterial PO2 and PCO2 which are sensed by the peripheral chemoreceptors located within the carotid and aortic bodies and by central chemoreceptors localised within the brain (Gonzalez et al., 1994; Daly, 1997; Nattie, 1999; Prabhakar, 2000). In adult mammals type I (glomus) cells of the carotid body are the primary peripheral chemosensitive elements which detect changes in arterial PO2 (Gonzalez et al., 1994; Prabhakar, 2000) and transmit this information to the afferent nerve fibres of the carotid sinus nerve, which in turn relays to the brainstem respiratory centres to produce adaptive changes in ventilation. Levels of PCO2 are monitored predominantly by the central chemoreceptors localised within the medulla oblongata (primarily at, or in close proximity to, the ventral medullary surface [Loeschcke, 1982]), as up to 80% of the CO2-evoked ventilatory response is mediated by the action of CO2 at the brainstem chemosensitive sites (Heeringa et al., 1979).
Neuroscience and behavioral physiology, 2003
The aim of the present work was to identify the role of ATP acting on specific P2X receptors in t... more The aim of the present work was to identify the role of ATP acting on specific P2X receptors in the central mechanisms of thermoregulation. Immunohistochemical studies demonstrated that brainstem structures involved in controlling body temperature contained large number of nerve cells bearing P2X ATP receptors. Experiments on conscious rats involving intracerebroventricular administration of an ATP analog and P2X antagonists showed that both activation and blockade of central P2X receptors produced marked changes in body temperature. Analysis of the effects of these substances provided grounds for suggesting that ATP acting on P2X receptors fulfils an important function in the mechanisms of transmitting afferent information from peripheral thermal receptors to thermoregulatory centers in the brainstem with responsibility for heat loss, while in pyrogen-induced fever ATP acting on these receptors may be involved in the activity of the endogenous antipyretic system.
Neuroscience, 2001
The ventrolateral medulla has a critical role in the generation and patterning of respiration via... more The ventrolateral medulla has a critical role in the generation and patterning of respiration via an extensive network of respiratory neurones. We have investigated the effects of activating purinergic P2 receptors within the ventrolateral medulla of the anaesthetised rat on the overall pattern of respiratory activity. In addition, using immunohistochemical techniques, we have identified the subtypes of P2X receptors in the ventrolateral medulla. Unilateral microinjection of ATP into the ventrolateral medulla reduced in a dose-dependent manner, or abolished, resting phrenic nerve discharge recorded as an indication of central inspiratory drive. ATP also elicited increases in blood pressure and variable changes in heart rate. These effects were mimicked by microinjection of the P2X receptor agonist alpha,beta-methylene ATP into the ventrolateral medulla. Whilst microinjection of suramin, a P2 receptor antagonist, had no effect on resting cardiorespiratory variables it blocked the res...
The Journal of physiology, Jan 15, 1995
1. This investigation was initiated because activation of laryngeal afferents, either by electric... more 1. This investigation was initiated because activation of laryngeal afferents, either by electrical stimulation of the superior laryngeal nerve (SLN) or by natural stimulation of receptors in the laryngeal mucosa, results in a cardiorespiratory response comprising bradycardia, hypotension and apnoea (phrenic nerve activity was suppressed). This pattern of response is qualitatively equivalent to the response that is evoked on activation of the arterial baroreceptors. 2. Preliminary studies indicated that the effects of activating the SLN were suppressed during stimulation in the hypothalamic defence area (HDA) at points that also blocked the effects of baroreceptor stimulation. 3. Recordings were taken from seventy-two neurones localized within the ipsilateral nucleus tractus solitarii (NTS) whose activity was modified by SLN stimulation. Sixty neurones responded with an EPSP on SLN stimulation; nine of these had an inspiratory firing pattern. Five neurones were seen to receive an IP...
The Journal of physiology, Jan 15, 1995
1. In anaesthetized, paralysed and artificially ventilated cats, recordings have been made in the... more 1. In anaesthetized, paralysed and artificially ventilated cats, recordings have been made in the nucleus tractus solitarii (NTS) to assess further the role of this nucleus in mediating the cardiorespiratory responses that are elicited on stimulation within the hypothalamic defence area (HDA). 2. The responses of NTS neurones to stimulation in the hypothalamus were assessed, as were their patterns of evoked response to electrical stimulation of the sinus (SN), aortic (AN), superior laryngeal (SLN) and vagus (VN) nerves. 3. Stimulation in the HDA affected the activity of 110 NTS neurones (85 studied in intracellular and 25 studied in extracellular recordings). The present study focused on those sixty-eight neurones that were excited by such stimulation (51 intracellular recordings and 17 extracellular recordings). 4. Of the sixty-eight neurones that were excited by HDA stimulation, seven revealed no changes in membrane potential or evoked discharge (2 neurones) but the stimulus facil...
The Journal of physiology, 1994
1. In order to assess the importance of the parabrachial nuclei in modulating cardiorespiratory a... more 1. In order to assess the importance of the parabrachial nuclei in modulating cardiorespiratory activity, electric current or microinjections of glutamate were used to stimulate discrete regions of the parabrachial nuclei in anaesthetized rats. 2. Stimulation of cell bodies in the medial region of the parabrachial nuclei and in the Kölliker-Fuse nuclei, caused an expiratory facilitatory response. This consisted mainly of a decrease in respiratory rate as measured by observing phrenic nerve activity. 3. Stimulation of cell bodies in the lateral region of the parabrachial nuclei caused an inspiratory facilitatory response. This consisted mainly of an increase in respiratory rate. 4. At the majority of sites (16 out of 20) where changes in respiratory rate were elicited by glutamate injection or electrical stimulation an increase in blood pressure was observed. The coexistence of increases in blood pressure and heart rate indicates the presence of inhibition of the heart rate component...
Journal of the autonomic nervous system, 1981
The excitability of vagal and carotid sinus nerve afferent terminals within the nucleus of the tr... more 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.
The Journal of experimental biology, 1982
Archives italiennes de biologie, 1974