PubMed Health⌕ Search

Biomedical subjects

R B Felder

Publications and source records attributed to R B Felder.

34 records · Page 2Linked to original sources
PubMed1990

Synaptic mechanisms regulating cardiovascular afferent inputs to solitary tract nucleus.

This brief review summarizes recent electrophysiological studies concerning the initial processing of cardiovascular afferent inputs within the central nervous system. This work has shown that the site of termination of baroreceptor afferent fibers, the nucleus of the tractus solitarius (nTS), is much more than a simple relay station. Interactions between afferent inputs from different reflexogenic areas and interactions that depend on the timing of the afferent inputs can influence the output of nTS neurons in either an inhibitory or facilitatory manner and thereby determine the signal that these neurons relay to subsequent central nuclei involved in cardiovascular regulation. In addition, descending inputs from more rostral structures (e.g., the hypothalamic defense area and the parabrachial nucleus) can further alter the responsiveness of nTS neurons to baroreceptor inputs. The evidence suggests that the neural substrates exist for a modulation of baroreflex gain at an early stage in the reflex pathway.

Afferent Pathways↗
PubMed1989

Alpha 2-adrenergic modulation of synaptic excitability in the rat nucleus tractus solitarius.

These studies examined the effects of the alpha-adrenergic agonist clonidine on spontaneous and synaptically evoked activity in the solitary tract nucleus in superfused rat brain slices. In one group of neurons which showed no spontaneous spike activity (n = 27), clonidine superfusion induced a dose-dependent increase of postsynaptic responsiveness to input from the ipsilateral solitary tract. In another group of neurons which were spontaneously active but unresponsive to tract input (n = 20), clonidine induced a dose-dependent depression of spontaneous discharge. A third group of neurons which were both spontaneously active and responsive to tract input (n = 11) showed primarily a depression of both activities. The neuronal responses to clonidine in all 3 groups were selectively blocked by the alpha 2-adrenoceptor antagonist yohimbine but not by the alpha 1-antagonist prazosin. These results provide insight into the possible actions of endogenous adrenergic systems in the synaptic processing of afferent sensory information within the solitary tract nucleus.

Action Potentials↗
PubMed1989

Alpha-adrenergic influences on neuronal responses to visceral afferent input in the nucleus tractus solitarius.

Studies were made of the effects of the alpha 1-adrenoceptor agonist methoxamine on spontaneous and synaptically evoked activity in the solitary tract nucleus in isolated, perfused slices of the brain of the rat and those effects were compared to the effects of the alpha 2-agonist clonidine. Methoxamine had no effect on the spike activity of 7 out of 8 spontaneously firing neurones, with no response to electrical stimulation of the solitary tract. Among neurones that responded to tract stimulation, those which were otherwise silent (N = 38) showed a decrease of responsiveness to tract input during the infusion of methoxamine, whereas those with spontaneous activity (N = 10) showed mostly increases of both firing rate and responsiveness. The effects of activation of alpha 2-receptors on responsiveness to tract stimulation were the opposite of previously demonstrated effects of activation of alpha 2-receptors, and these opposing effects could be demonstrated in the same neurone. These results suggest that the transmission of visceral sensory information within the nucleus tractus solitarius may be controlled by opposing alpha 1- and alpha 2-receptor-mediated neural systems.

Animals↗
PubMed1988

Excitatory amino acid receptors intrinsic to synaptic transmission in nucleus tractus solitarii.

Excitatory amino acid (EAA) receptors are present in the nucleus tractus solitarii (NTS), and there is growing evidence that L-glutamate (L-Glu) may activate neurons in this region to precipitate changes in autonomic discharge. To evaluate the potential role of EAA agonists in synaptic transmission in NTS, we studied the responses of single units in an in vitro brain slice preparation of NTS to electrical stimulation of one or both solitary tracts (TS) before, during and after superfusion with selected EAA antagonists. Dose-response studies demonstrated that the synaptic input to NTS units was substantially blocked by 2-amino-5-phosphonovaleric acid (APV) at perfusion concentrations of 1 mM, by kynurenic acid (KYN) at 10 mM, and glutamate diethylester (GDEE) at 10 mM. Using these concentrations, we examined the responses of single NTS neurons to afferent input from ipsilateral and contralateral TS stimulation before, during and after perfusion with each antagonist. KYN inhibited afferent input from one TS but not the other in 7 of 13 cells tested, inhibited both inputs in 4, and caused differential augmentation of input in two. APV caused differential inhibition of the two inputs in 4 of 9 cells tested, differential excitation in 1 and inhibition of both inputs in one. GDEE caused differential inhibition in 4 of 9 cells tested, differential excitation in 3 and inhibition of both inputs in one. When inputs from a single TS were examined, those blocked by APV were always blocked by KYN (5 of 16 inputs tested); there was overlap between the blocking effects of KYN and GDEE (4 of 12 inputs tested) and occasionally of APV and GDEE (one of 12 inputs tested). We also observed differential blocking effects of these agents on single inputs to the same neuron. Evoked responses were reduced or enhanced by only one of the two agents for 5 of 16 inputs tested with KYN and APV, 4 of 12 tested with KYN and GDEE, and 7 of 12 tested with APV and GDEE. The average reduction in synaptically evoked responses caused by blocking doses of antagonist was 85 +/- 6% for KYN, 63 +/- 28% for APV and 68 +/- 10% for GDEE. These data indicate that all 3 major EAA antagonists can selectively inhibit electrically evoked afferent input to NTS neurons and suggest a role for specific EAA receptors in mediating input to these neurons over different afferent pathways.

2-Amino-5-phosphonovalerate↗
PubMed1988

Stimulation of parabrachial neurons elicits a sympathetically mediated pressor response in cats.

We examined the role of the parabrachial neuronal mass in mediating the pressor response to electrical stimulation of parabrachial nucleus (PBN). In anesthetized cats, 100 mM L-glutamate (L-glu) was microinjected into PBN at sites from which low-intensity (25 microA) electrical stimulation evoked a pressor response. Arterial pressure, heart rate, and, in some animals, renal or phrenic nerve activity were monitored. Microinjection of L-glu caused an increase in arterial pressure that was comparable with that elicited by low-intensity electrical stimulation. Electrical stimulation, and to a lesser extent L-glu microinjection, caused an increase in renal sympathetic nerve activity but no significant change in heart rate. No consistent change in central respiratory drive accompanied the pressor response. These responses were preserved after baroreceptor denervation but were blocked by intravenous administration of the alpha-adrenergic receptor antagonist phentolamine. Microinjection into PBN of 2 mM kainic acid, which selectively depolarizes neurons but spares axons, reversibly blocked the arterial pressure and renal nerve responses to the 25-microA electrical stimulus. We conclude that the pressor response elicited by electrical stimulation of PBN in the anesthetized cat is mediated by cellular elements in PBN, not by fibers of passage. Because phentolamine completely blocked the pressor response, we suggest that it is subserved peripherally by sympathetic alpha-adrenergic rather than humoral (e.g., angiotensin, vasopressin) vasoconstrictor mechanisms. Finally, our data indirectly suggest that PBN stimulation may differentially engage efferent components of the sympathetic nervous system to elicit the pressor response.

Animals↗
PubMed1988

An intracellular study of time-dependent cardiovascular afferent interactions in nucleus tractus solitarius.

1. We used a model of bilateral carotid sinus nerve (CSN) stimulation to investigate cardiovascular afferent interactions in nucleus tractus solitarius (NTS) in anesthetized cats. In some instances, interactions with afferent inputs from vagus or renal nerves were also examined. 2. Intracellular recordings were made from 88 NTS neurons activated by electrical stimulation of one or both CSNs. Excitatory (EPSPs), inhibitory (IPSPs), and combined excitatory and inhibitory (EPSP/IPSP) postsynaptic membrane potential responses to ipsilateral CSN stimulation were observed. The input from opposite CSN (30 of 34 neurons tested) or from other ipsilateral afferent sources (vagus nerve, 10 tested; renal nerve, 9 tested) was qualitatively the same as that from ipsilateral CSN. 3. Conditioning tests demonstrated that the response (EPSP, IPSP, or EPSP/IPSP) evoked by a test stimulus to one CSN was reduced in amplitude and/or duration by a prior stimulus (1-5 pulses) to the same (82 of 85 neurons) or to the opposite (30 of 37 neurons) CSN at conditioning intervals ranging from 50 to 550 ms. For cells in which CSN stimulation evoked an EPSP, this inhibitory interaction occurred with no change in resting membrane potential and no change in input resistance. For cells in which CSN stimulation evoked an IPSP, the inhibitory interaction persisted beyond the duration of the CSN evoked IPSP. 4. We infrequently (3 cells) observed an excitatory interaction, in which the conditioning stimulus resulted in rhythmic depolarization of the neuron and a facilitated action potential response to an appropriately timed test stimulus. 5. During continuous CSN stimulation, postsynaptic potentials (PSPs) evoked by ipsilateral CSN were abolished in the steady state at stimulus frequencies of 5-20 Hz (n = 14). In cells that received a convergent input from contralateral CSN, the PSP evoked by contralateral CSN was usually (6 of 8 tested) abolished at lower stimulus frequencies (median difference = 5.0 Hz). 6. We conclude that individual NTS neurons frequently have the same PSP response to peripheral afferent inputs of different origins. Time-dependent interactions among cardiovascular afferent inputs that evoke PSPs of like kind may determine the nature of the integrated signal conveyed from NTS to subsequent cardiovascular related central nuclei. Both inhibitory and, less frequently, excitatory time-dependent interactions between cardiovascular afferent inputs occur. The absence of membrane potential changes associated with the inhibitory interaction suggests it may be mediated by disfacilitation.

Animals↗
PubMed1988

Modulation of carotid sinus afferent input to nucleus tractus solitarius by parabrachial nucleus stimulation.

There is increasing evidence that the parabrachial nucleus (PBN) may be integrally involved in cardiovascular reflex regulation. In cats in which anesthesia was induced with pentobarbital and maintained with alpha-chloralose, we studied the effects of PBN stimulation on cardiovascular afferent inputs to nucleus tractus solitarius (NTS), the site of first central termination for cardiovascular afferent fibers. Electrical stimulation of PBN resulted in an initial excitation followed by prolonged inhibition of the spontaneous activity of NTS neurons activated by ipsilateral carotid sinus nerve (CSN) stimulation. In 53 units recorded extracellularly in and around NTS, the number of action potential responses to ipsilateral CSN stimulation was reduced 73 +/- 3% by a prior conditioning stimulus to PBN at an interval of 30-60 msec. CSN input to 10 units excited by selective baroreceptor stimulation was inhibited by the PBN conditioning stimulus, as were convergent inputs from contralateral CSN, vagus, and renal nerves. The inhibitory influence of the PBN stimulus lasted as long as 450 msec. We examined the mechanism for these phenomena in additional intracellular recording experiments. In 57 units, PBN stimulation evoked a long lasting (65-359 msec) membrane potential hyperpolarization. In 42 cells, the PBN evoked inhibitory postsynaptic potential (IPSP) was preceded by an excitatory postsynaptic potential (EPSP). CSN and convergent inputs were inhibited when timed to occur during the PBN induced IPSP. Conversely, CSN and convergent afferent nerves inhibited PBN input to NTS neurons with no associated change in membrane potential (n = 9 of 14). These data demonstrate for the first time a potent modulatory influence of PBN on NTS neurons processing cardiovascular afferent input.

Afferent Pathways↗
PubMed1987

Interactions in nucleus tractus solitarius between right and left carotid sinus nerves.

Bilateral carotid sinus nerve stimulation was used as a model for studying cardiovascular afferent interactions in the nucleus tractus solitarius (NTS) region of dorso-medial medulla. Extracellular action potential recordings were made from 69 single units, 33 of which were excited independently by both right and left carotid sinus nerves (CSNs). Fifteen of these were located in NTS. Peak latencies to electrical stimulation of NTS neurons were 17.7 +/- 2.1 ms to ipsilateral CSN and 20.9 +/- 1.5 ms to contralateral CSN. Summation of afferent input was routinely demonstrated. In 10 units in NTS, a conditioning stimulus applied to one CSN caused prolonged inhibition of the response to a test stimulus to the same or the other CSN. The duration of inhibition was dependent on the intensity of the conditioning stimulus, not on prior excitation of the unit by the conditioning stimulus. In five additional excitability testing experiments, we found limited evidence to suggest that primary afferent depolarization of the central fibers of one CSN by stimulation of the contralateral CSN might be contributing to this inhibitory interaction. The data suggest that the outcome of integrative interactions between right and left CSN inputs to NTS neurons may depend largely on the temporal sequence of convergent afferent impulses.

Action Potentials↗
PubMed1986

Excitatory and inhibitory interactions among renal and cardiovascular afferent nerves in dorsomedial medulla.

Central interactions between renal afferent nerves (RN) and carotid sinus (CSN) and aortic (AN) nerves were investigated by recording extracellular action potentials from single units in and around the nucleus tractus solitarius (NTS) in alpha-chloralose-anesthetized cats. Forty-nine units were activated by electrical stimulation of the renal nerve; twenty-seven of these also were excited by CSN, AN, or both. Summation of inputs was demonstrated during simultaneous subthreshold or suprathreshold stimulation of RN and CSN or AN. In 10 units excited by simultaneous stimulation of RN and AN or CSN, a conditioning stimulus (333 Hz for 10 ms) applied to RN caused prolonged (up to 150 ms) inhibition of responses to stimulation of AN or CSN; reciprocal inhibitory interactions were also shown. These studies show that renal afferent input interacts with cardiovascular afferent input at neurons in the NTS region of dorsal medulla and suggest that the outcome of these interactions at the single cell level may be critically dependent on the temporal relationships among afferent impulses converging on common central synapses.

Afferent Pathways↗
PubMed1985

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↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

Reflex modulation of carotid sinus baroreceptor activity in the dog.

Carotid sinus baroreceptor (CBR) sensitivity may be increased by electrical stimulation of sympathetic nerves passing to the carotid sinus region. It remains unknown if reflexly induced changes in efferent sympathetic discharge affect CBR function. In 17 anesthetized dogs, we reflexly induced alterations in sympathetic discharge and recorded CBR activity originating from a vascularly isolated carotid sinus. The stimulus to the baroreceptors was pulsatile with constant mean and pulse pressure. Occlusion of the contralateral common carotid artery (n = 6) resulted in a reflex increase in arterial pressure (116 +/- 10 to 153 +/- 14 mmHg) and an increase (121 +/- 2% of control) in baroreceptor activity (P less than 0.05). Inferior vena caval occlusion (n = 6), which induced a reduction in arterial pressure (145 +/- 19 to 75 +/- 21 mmHg), also provoked an increase (141 +/- 10% of control) in baroreceptor discharge (P less than 0.05). Raising pressure (to 200 mmHg) in the contralateral carotid sinus (n = 7) resulted in a reflex decrease in arterial pressure (169 +/- 16 to 129 +/- 13 mmHg) and a reduction (82 +/- 3% of control) in baroreceptor activity (P less than 0.05). The changes in baroreceptor discharge were abolished by ipsilateral cervical sympathectomy or ganglionic blockade (n = 4). Our findings demonstrate that reflexly induced alterations in the activity of sympathetic fibers innervating the carotid sinuses can modulate baroreceptor discharge.

Animals↗
PubMed1982

Responses to activation of cardiac sympathetic afferents with epicardial bradykinin.

The cardiovascular reflex responses mediated by cardiac sympathetic afferent fibers (CSA) appear to differ depending on the nature of the activating stimulus. Although electrical stimulation of CSA may result in either excitatory of inhibitory reflex responses in both cats and dogs, topical application of bradykinin to these sensory endings elicits only excitatory reflex responses in cats. The present experiments were performed to determine whether CSA activated by epicardial bradykinin also mediate solely excitatory reflex responses in the dog. The changes in efferent cardiac or renal sympathetic nerve activity, mean arterial pressure, and heart rate resulting from application of bradykinin to the left ventricular epicardial surface were determined in 15 chloralose-anesthetized, sinoaortic-denervated vagotomized dogs. Activation of CSA with bradykinin (0.1--120 g/ml) elicited inhibitory responses in eight dogs, excitatory responses in four dogs, and biphasic responses in three dogs. Both excitatory and inhibitory reflexes were eliminated by cardiac sympathetic afferent denervation. The results show that, in the dog, cardiac receptors with sympathetic afferent fibers activated by epicardial bradykinin mediate nonuniform reflex responses that tend to be predominantly inhibitory.

Action Potentials↗
PubMed1981

The cardiocardiac sympathetic reflex during coronary occlusion in anesthetized dogs.

Cardiac sympathetic afferent fibers activated during coronary occlusion exert an excitatory influence on sympathetic discharge to the heart in cats after spinal cord section. The significance of this cardiocardiac sympathetic reflex response during myocardial ischemia in animals with an intact neuraxis is unknown. We studied the responses of efferent cardiac sympathetic nerve activity (CSNA), arterial pressure, and heart rate to coronary occlusion in two groups of dogs with cardiac sympathetic reflexes intact and with other reflex inputs affecting CSNA sectioned or controlled. In group I (n = 10), the vagi were sectioned, the spinal cord remained intact, and the carotid sinuses were isolated and perfused to maintain baroreceptor input constant. Coronary occlusion was performed at moderate and low basal levels of CSNA by setting carotid sinus pressure at 125-150 and 200 mm Hg, respectively. Under these conditions, CSNA was not altered by occlusion of either the anterior descending or the circumflex coronary artery. In group II (n = 4), the vagi were sectioned and the spinal cord was interrupted. In these dogs, CSNA increased significantly (61 +/- 19%) during coronary occlusion. These results show that an excitatory cardiocardiac sympathetic reflex can be demonstrated in dogs with spinal cords sectioned but not with spinal cords intact. This finding is consistent with the view that inhibitory bulbospinal pathways minimize the influence of the spinal cardiocardiac sympathetic reflex during myocardial ischemia in anesthetized dogs.

Animals↗