Biomedical subjects

J F Paton

Publications and source records attributed to J F Paton.

66 records · Page 4Linked to original sources

PubMed1991

Efferent connections of lobule IX of the posterior cerebellar cortex in the rabbit--some functional considerations.

The Purkinje cell projection from the cardiovascular region of sublobule b of the uvula (medial area of zone A) has been investigated using anterograde tracing methods in the rabbit. The importance of the integrity of the identified pathways in mediating the cardiovascular responses from the uvula has been studied in subsequent lesioning experiments. Wheat germ agglutinin-conjugated horseradish peroxidase or tritiated amino acids were microinjected into sublobule IXb. This resulted in anterogradely labelled Purkinje cell axons in both the inferior and superior cerebellar peduncle. In agreement with previous studies in rabbit we also found labelled fibres at the level of the fastigial nucleus and vestibular complex. However, the labelled fibres we observed in the parabrachial nucleus have not been reported in previous studies except in the prosimian primate. Projections from IXb showed terminal-like patterns of label in the ventromedial region of the caudal fastigial nucleus, the dorsal areas of the superior and inferior vestibular nuclei and in the medial and lateral divisions of the parabrachial nucleus. Labelled fibres were also seen coursing in the lateral vestibular nucleus. Lesioning experiments have revealed that the integrity of the superior cerebellar peduncle is essential for the expression of the cardiovascular responses (bradycardia and depressor response) elicited from the uvula in the anaesthetized rabbit. In contrast, the pattern of cardiovascular response evoked in a decerebrate rabbit (tachycardia and pressor response) was abolished when the inferior cerebellar peduncle was lesioned.

Amino Acids↗

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

Tonically rhythmic neurons within a cardiorespiratory region of the nucleus tractus solitarii of the rat.

1. Accumulated evidence from the literature led us to investigate whether centrally generated activity was present within a central neuronal network for cardiovascular control. An in vitro approach using a brain stem slice preparation was employed to study the cardiorespiratory region of the nucleus of the solitary tract (NTS) in the rat. 2. We have discovered rhythmically active neurons within a restricted part of the cardiorespiratory NTS. These neurons were localized to regions directly medial and dorsomedial to the solitary tract (ts) at levels 0.2 mm rostral to obex extending caudally to the rostral part of the commissural subnucleus, an area considered to be concerned with cardiovascular regulation. Although other subnuclei were explored for neurons with ongoing activity (i.e., dorsolateral, dorsal, and interstitial) at levels 1.5 mm caudal to 0.75 mm rostral to obex, we failed to find similarly tonically active cells. 3. Intra- or extracellular recordings were made from 85 neurons with a mean firing rate of 5.1 +/- 0.3 (SE) Hz (range 1-15). The majority of these (n = 75) received an excitatory synaptic input from the ipsilateral ts, with latencies ranging between 4 and 20 ms. 4. To determine whether the tonically rhythmic cells were dependent on synaptic excitatory drives or were inherent to the cell, we tested, in 45 neurons recorded extracellularly, the effect of blocking synaptic inputs mediated by excitatory amino acids by applying either DL-2-amino-5-phosphonovaleric acid [APV; N-methyl-D-aspartate (NMDA) antagonist] or MK-801 (NMDA antagonist) with kynurenic acid (Kyn; NMDA, quisqualate, and kainate receptor blocker) to the bath. After bath application of APV and Kyn or MK-801 and Kyn, two different responses were observed. In 19 cells ongoing rhythmic activity was unperturbed, but firing was completely silenced in 26 neurons. In all cases neurons failed to respond to glutamate delivered locally, and the synaptic input evoked from the ts was blocked. This evidence indicates the existence of two cell types: autoactive (AA) or pacemaker-like neurons, the discharge pattern of which depends on intrinsic properties, and synaptically driven (SD) neurons, the activity of which is driven by synaptic inputs. 5. Cobalt chloride (Co) was used to block synaptic effects and was found to increase the discharge rate of AA neurons by 9.9 Hz on average (i.e., cells resistant to APV and Kyn or MK-801 and Kyn). However, the rhythmic activity of cells previously silenced with excitatory amino acid antagonists (i.e., SD cells) was also abolished in the presence of Co.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

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

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↗

PubMed1990

Nucleus tractus solitarius as mediator of evoked parabrachial cardiovascular responses in the decerebrate rabbit.

1. The present study has assessed the importance of neurones within the nucleus tractus solitarius (NTS) in mediating the cardiovascular response evoked from the parabrachial nucleus (PBN) in the decerebrate rabbit. Microinjection techniques were employed so that the magnitude of the circulatory responses elicited from the PBN could be compared before, and after, kainic acid or bicuculline were microinjected into restricted regions of the NTS. 2. Electrical stimulation of the PBN (both medial and lateral regions) evoked variable changes in heart rate, a pressor response, vasoconstriction in the hindlimb and an increase in renal sympathetic nerve activity. Glutamate injected into these regions of the PBN elicited a similar pattern of response except that a tachycardia was observed consistently. 3. Both electrical and chemical stimulation of restricted regions of the NTS evoked bradycardia and a depressor response together with an increase in femoral vascular conductance and an inhibition of activity in the renal nerve. 4. Chemical lesions placed in these regions of the NTS by microinjecting kainic acid were found to attenuate both the heart rate and arterial blood pressure responses elicited from sites in the medial and lateral PBN using either electrical or chemical stimulation. Equivalent effects were produced on microinjecting the GABAa receptor antagonist bicuculline into the NTS. 5. These data indicate that NTS neurones play a part in mediating the cardiovascular responses that are evoked from the PBN and suggest that the action of the PBN at the level of the NTS is mediated via a GABAergic mechanism.

Animals↗

PubMed1987

The cardiovascular responses elicited from the posterior cerebellar cortex in the anaesthetized and decerebrate rabbit.

1. In this study the posterior cerebellar cortex has been electrically stimulated and changes in heart rate, arterial blood pressure, regional blood flows and renal sympathetic nerve discharge have been recorded in both the anaesthetized and the decerebrate unanaesthetized rabbit. 2. Specifically, lobules VII, VIII, IX and X of the posterior cerebellar vermis were stimulated but the only region which elicited cardiovascular changes was lobule IX (the uvula). The responsive area of the uvula was localized to the medial regions of sublobules a, b and c and was identical in both anaesthetized and decerebrate animals. 3. Under urethane anaesthesia, uvula stimulation evoked a small bradycardia, a fall in arterial pressure, a transient inhibition of renal sympathetic nerve activity, with no change in renal vascular conductance, and an increase in femoral vascular conductance. 4. Stimulation of an identical area in the decerebrate rabbit evoked a marked tachycardia, an increase in blood pressure, maintained increase in renal sympathetic nerve discharge, and decreases in both renal and femoral conductances. 5. The response evoked from the decerebrate rabbit could be reversed by a small dose of anaesthetic to a pattern of response which was essentially identical to that seen in the urethane-anaesthetized rabbit. 6. This influence of anaesthetics on the pattern of cardiovascular responses that may be elicited from the cerebellar cortex indicates that caution should be exercised when making physiological inferences on the basis of stimulation experiments in anaesthetized preparations. 7. In the light of the cardiovascular changes that may be evoked from the uvula, and recent neuroanatomical and neurophysiological data concerning afferent and efferent connexions of this cerebellar region, we discuss the possibility that the uvula plays a role in the alerting reaction of the rabbit.

Anesthesia, General↗

PubMed1987

Cardiovascular and phrenic nerve responses to stimulation of the amygdala central nucleus in the anaesthetized rabbit.

1. The cardiovascular responses to electrical stimulation of the central nucleus of the amygdala (c.n.) have been studied in chloralose-anaesthetized rabbits. A pattern of response involving bradycardia, hypotension and hind-limb vasodilatation, accompanied by an increase in the rate of phrenic nerve discharge, was evoked only in response to stimulation within the medial portion of the c.n. 2. The cardiovascular responses were not secondary to the changes in respiratory activity since they were unaffected by altering central respiratory drive by either hypo- or hyperventilation of the animal. 3. The bradycardia was attenuated by the administration of atropine sulphate and abolished by the subsequent administration of propranolol, which when given alone attenuated the bradycardia. Atropine or propranolol given alone also attenuated the hypotension evoked by medial c.n. stimulation but the concurrent hind-limb vasodilatation was unaffected. 4. Atenolol, which unlike propranolol does not cross the blood-brain barrier, had little effect on the bradycardia in response to medial c.n. stimulation, but the subsequent administration of atropine abolished it. The hypotension in response to medial c.n. stimulation was also unaffected by atenolol. 5. The vasodilatation in response to medial c.n. stimulation was abolished by administration of guanethidine even after restoration of hind-limb perfusion pressure to control values by the infusion of angiotensin II into the hind-limb perfusion circuit. 6. Electrical stimulation of areas within 0.5 mm of the medial c.n. also resulted in bradycardia but then it was accompanied by hypertension and hind-limb vasoconstriction. Stimulation of areas 1.0 mm distant to the medial c.n. resulted in small and inconsistent cardiovascular responses. 7. These results show that hind-limb vasodilatation, mediated by withdrawal of sympathetic tone, occurs in response to stimulation within the medial c.n. of the rabbit and is in part responsible for the observed hypotension. It has also been confirmed that the bradycardia in response to medial c.n. stimulation is mediated by the vagus nerves.

Action Potentials↗

PubMed1987

Cardiovascular responses evoked from the fastigial region of the cerebellum in anaesthetized and decerebrate rabbits.

1. The rostral and caudal regions of the fastigial nucleus (f.n.) in both anaesthetized and decerebrate rabbits have been stimulated electrically while monitoring phrenic nerve activity, heart rate, blood pressure and blood flow to the kidney and hindlimb in addition to recording renal sympathetic nerve activity. 2. Stimulation of the rostral region of the f.n. in the anaesthetized and decerebrate rabbit produced a silencing of phrenic nerve discharge, either no change in heart rate or a vagally mediated bradycardia and a pressor response associated with vasoconstriction in both renal and femoral beds which resulted from an increase in sympathetic vasomotor tone. 3. Stimulation of the caudal region of the f.n. in the anaesthetized rabbit evoked apnoea and a bradycardia which was partially attenuated by vagal blockade. Also, a depressor response was obtained with no change in renal vascular resistance, a transient inhibition of renal sympathetic nerve discharge and a vasodilation in the hindlimb resulting from the withdrawal of sympathetic vasoconstrictor tone. In contrast, electrical stimulation of the same site in the unanaesthetized decerebrate rabbit evoked an increase in central inspiratory drive, a tachycardia and a pressor response with vasoconstriction in both vascular beds. The cardiac and vascular responses were abolished after sympathetic blockade. 4. Administration of a small dose of anaesthetic to the decerebrate preparation did not affect the direction of the cardiovascular or central respiratory responses evoked from the rostral f.n. but reversed the pattern of response elicited from the caudal f.n. to that seen in the intact anaesthetized rabbit. 5. The results of the present study suggest the existence of two separate regions associated with the f.n. which can influence the cardiovascular system in the rabbit. Furthermore, it would seem that the cardiovascular responses evoked from the vicinity of the caudal and rostral poles of the f.n. are mediated by two distinct pathways which might suggest two separate functional roles for the cerebellum in cardiovascular control in the rabbit.

Anesthesia, General↗

PubMed1987

Cardiovascular and respiratory responses evoked from the posterior cerebellar cortex and fastigial nucleus in the cat.

1. In both anaesthetized and decerebrate cats the cerebellar cortex (lobules VI, VII, VIII, IX and X) and the fastigial nucleus (f.n.) have been stimulated electrically, and chemically, while recording changes in phrenic nerve discharge, heart rate, arterial blood pressure and renal and femoral blood flow. 2. Stimulation of lobules VI, VII, VIII and Xb failed to elicit any cardiovascular or respiratory changes. Activation of lobule IX (the uvula), and in some preparations sub-lobule Xa, evoked cardiovascular and respiratory responses consistently. In the anaesthetized cat, electrical stimulation of the uvula evoked apnoea, a small bradycardia and a depressor response associated with vasodilatation in the hindlimb vascular bed. In contrast, stimulation in an equivalent region in a decerebrate preparation elicited an apneustic discharge, a pronounced tachycardia and a rise in arterial pressure with vasoconstriction in both renal and femoral vascular beds. In both the anaesthetized and decerebrate animals the pattern of response elicited by chemical activation was identical to that seen with electrical stimulation. 3. Electrical, or chemical, stimulation after administration of anaesthetic to the decerebrate cat then evoked an identical pattern of response to that seen in the 'intact' anaesthetized animal. This evidence suggests that the reversal in the pattern of the response in an effect of the anaesthetic agent and not the decerebration itself. 4. The only area of the f.n. to produce cardiovascular effects was the rostral region. Electrical stimulation of the rostral f.n. in both anaesthetized and decerebrate preparations inhibited central inspiratory activity and evoked tachycardia, along with a pressor response associated with vasoconstriction in both renal and femoral vascular beds. In contrast, chemical excitation of those sites in the rostral f.n. shown previously to produce pronounced cardiovascular and respiratory changes failed to elicit any changes in the recorded variables. 5. The present evidence suggests that there are two areas in the cat cerebellum which can exert pronounced cardiovascular and respiratory effects. The patterns of response elicited by electrical stimulation of the posterior cortex and rostral f.n. are mediated by two separate cerebellar-brainstem pathways as judged by the two different effects of anaesthesia on the evoked responses. We suggest that the f.n. may not play a role in the control of the cardiovascular system since chemical excitation of cell bodies of the rostral f.n. failed to elicit the so-called 'fastigial pressor response'.

Anesthesia, General↗

PubMed1987

Effects of stimulation of nasal and superior laryngeal inputs on the hindlimb vasculature of anaesthetized cats.

1. In chloralose-anaesthetized artificially ventilated cats, either stimulation of the nasal mucosae with water or electrical stimulation of the superior laryngeal nerve (s.l.n.) resulted in apnoea, as measured from the phrenic nerve activity, and a rise in perfusion pressure of a hindlimb perfused at constant flow. In the absence of changes in venous pressure this vascular response would indicate vasoconstriction in the hindlimb. There was, however, no significant change in either heart rate or arterial blood pressure. 2. Simultaneous stimulation of the nasal mucosae and s.l.n. also resulted in apnoea but with a larger hindlimb vasoconstriction than was obtained with stimulation of only one input. This increased vasoconstriction was not significantly different from the one which in theory could be obtained by summing the two individual responses from stimulation of the nasal mucosae or s.l.n. 3. In cats anaesthetized with chloralose-urethane, stimulation of the nasal mucosae or s.l.n. also evoked an apnoea and hindlimb vasoconstriction. However, in these animals this was accompanied by a bradycardia and small fall in arterial blood pressure. 4. The present results show that whilst stimulation of two parts of the upper respiratory tract evokes qualitatively similar responses in the hindlimb vasculature, simultaneous activation of the two stimuli does not appear to result in facilitation of this hindlimb vasoconstrictor response, simply an addition of those obtained on separate stimulation. The bradycardia evoked in response to upper airway stimulation is dependent on the anaesthetic used and in the present experiments could only be obtained in animals anaesthetized with choralose-urethane.

Anesthesia, General↗