Convergence properties of solitary tract neurons responsive to cardiac receptor stimulation in the anesthetized cat.

The convergence pattern of cardiac receptors, pulmonary C-fibers, carotid chemoreceptor, and baroreceptor afferents onto neurons within the nucleus of the solitary tract (NTS) was studied in the anesthetized (pentobarbitone sodium, 40 mg/kg,) paralyzed and artificially ventilated cat. Extra- and intracellular recordings were made from NTS neurons while stimulating both cardiac receptors by aortic root injections of veratridine (1-3 micrograms/kg) and pulmonary C-fibers by a right atrial injection of phenylbiguanide (10-20 micrograms/kg). The ipsilateral carotid body was stimulated by using arterial injection of CO2-saturated bicarbonate solution, whereas inflation of the ipsilateral carotid sinus was used to activate baroreceptors. The ipsilateral cardiac vagal branch, cervical vagus, and carotid sinus nerves were stimulated electrically (1 Hz, 0.2-1 ms, 1-35 V). In 78 NTS neurons recorded either extracellularly (n = 47) or intracellularly (n = 31), electrical stimulation of the cardiac branch of the vagus nerve evoked synaptic potentials (spikes and/or excitatory postsynaptic potentials) with an onset latency between 4 and 220 ms. Some neurons displayed both short and long latency inputs(15.5 +/- 1.8 and 160.0 +/- 8.5 ms; n = 14). Of these 78 neurons, 24 responded to veratridine stimulation of cardiac receptors (i.e., cardioreceptive neurons) by exhibiting an augmenting-decrementing discharge of 37 +/- 4 s in duration with a peak frequency of 30 +/- 5 Hz. Convergence from other cardiorespiratory receptors was noted involving either carotid chemoreceptors (n = 7) or pulmonary C-fibers (n = 4) or from both carotid chemoreceptors and pulmonary C-fibers (n = 6). In contrast, only one cardioreceptive NTS neuron was activated by distension of the carotid sinus. Recording sites recovered were confined to the medial NTS at the level of the area postrema and extended caudally into the commissural subnucleus. Our results indicate a convergence of carotid chemoreceptor and pulmonary C-fiber afferent inputs to cardioreceptive NTS neurons. With the paucity of baroreceptor inputs to these neurons it is suggested that sensory integration within the NTS may reflect regulatory versus defensive or protective reflex control.

Hypothalamic modulation of laryngeal reflexes in the anaesthetized cat: role of the nucleus tractus solitarii.

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 IPSP on SLN stimulation. 4. Five respiratory SLN-activated neurones were unresponsive to stimulation of the other nerve inputs, whilst four received convergent EPSP inputs on sinus nerve (SN) stimulation. One cell of these four also received inputs from the aortic and the vagus nerves. Sixty-one non-respiratory SLN-activated neurones also received convergent inputs from the sinus nerve. Of these, fifty displayed an EPSP, four an IPSP and seven an EPSP-IPSP. Fifteen neurones also received inputs from the aortic nerve and seventeen from the vagus. 5. From the population of neurones affected by SLN stimulation, twenty-four of seventy were also influenced by HDA stimulation (3 were respiratory cells). Sixteen of these responses consisted of an EPSP (2 respiratory cells), five of an IPSP (1 respiratory cell) and three of an EPSP-IPSP. 6. In neurones receiving an IPSP on HDA stimulation, the SLN-evoked excitatory response was reduced throughout the period of HDA-evoked inhibition. These neurones were all shown to receive excitatory inputs from the arterial baroreceptors and laryngeal mechanoreceptors. 7. Additionally, in the thirty-seven neurones that were excited by SLN stimulation but received no direct synaptic input on HDA stimulation, a conditioning stimulus to the HDA evoked a block of SLN-evoked responses without an accompanying change in membrane potential. Several of these neurones were also affected by both baroreceptor and laryngeal mechanoreceptor stimulation. 8. These observations are discussed in the context of the role of the NTS in cardiorespiratory control. The potential importance of these interactions in respiratory distress are highlighted and the implications for the organization of central pathways for the control of autonomic and respiratory function are discussed.

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers.

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.

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.

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.

Hypothalamic control of nocireceptive and other neurons in the marginal layer of the dorsal horn of the medulla (trigeminal nucleus caudalis) in the rat.

The effect of electrical stimulation of the preoptic area of the hypothalamus on the discharge of neurones in the marginal layer (lamina I) of the trigeminal nucleus caudalis was studied in the anaesthetised rat. There was a powerful suppression of the discharge evoked by noxious thermal stimuli in 49/49 specific nociceptor driven (nocireceptive) neurones. The inhibitory effect increased with graded increases in the intensity of preoptic stimulation. Stimulation, however, produced only a small reduction in the discharge of 14/17 cold receptive neurones. Thresholds for producing suppression of cold receptive neurones were generally higher than those for nocireceptive neurones. There was no effect on the activity of 12/12 low threshold mechanoreceptive neurones. The inhibitory action generated on the activity of nocireceptive neurones was reduced by electrolytic lesions in the nucleus raphe magnus (NRM) or the nucleus paragigantocellularis lateralis (PGCL) or the dorsolateral and ventrolateral periaqueductal gray matter (PAG). Lesions made in the ventral or dorsal aspect of PAG were, however, ineffective in reducing the suppression. It is suggested that the powerful descending inhibitory control of nociceptive transmission in the trigeminal nucleus caudalis is one of the neuronal mechanisms mediating analgesia from the preoptic area of the hypothalamus.

Medial hypothalamic stimulation produces analgesia to facial heating in unrestrained rats.

Gradual heating of the face in unrestrained conscious rats produced a behavioural response at a mean threshold temperature of 41.9 degrees C (S.E.M. +/- 0.02, 174 tests). This temperature did not change with tests repeated at 5-min intervals over one hour. During stimulation of the preoptic area of the hypothalamus the response temperature was consistently raised by about 3 degrees C but returned to the control level within 5 min.

Sensory processing in a thermal afferent pathway.

Extracellular recordings were made from cold-receptive afferent fibers in the trigeminal ganglion of rats anesthetized with halothane. By applying a standardized series of steady or changing temperatures to the receptive fields, we recorded the static and dynamic responses of the afferents. Comparable recordings were made from neurons in the marginal layer of the caudal trigeminal nucleus onto which the cold fibers synapse. The static and dynamic responses of the afferent fibers were reproduced faithfully by the second-order neurons, but at a much higher level of activity. Ganglionectomy silenced the second-order cells. Their continuous high level of activity appears to depend on the tonic input from the afferent fibers and not on any intrinsic circuits in the medulla.

Facial sensitivity to rates of temperature change: neurophysiological and psychophysical evidence from cats and humans.

The dynamic responses in a thermal afferent pathway to rates of temperature change have been studied in anaesthetized cats. Recordings were made in the caudal trigeminal nucleus from neurones with a synaptic input from facial cold receptors. Five rates of cooling and warming ranging from 0.05 degrees C/sec to 1 degree C/sec were applied to the receptive fields of the neurones. Several measures of the dynamic response were computed but the most representative was the maximum rate during cooling or the minimum rate during warming. During cooling the maximum rate increased with increasing cooling rates between 0.05 degrees C/sec and 0.25 degrees C/sec, but did not increase at faster rates. Minimum activity during warming reached near zero at rates of 0.25 degrees C/sec and faster. The total number of impulses generated during cooling or absent during warming was unrelated to rate of temperature change. The same thermal stimuli were applied to the cheeks of human subjects. They were able to sense cooling or warming changes at 0.05 degrees C/sec. They could also distinguish the faster of two cooling changes when these were slow, but not when they were fast. Warming rates could not be distinguished, except from an adapting temperature of 35 degrees C, when warm receptors would have been activated. There was good agreement between the responses of the cat neurones and the human sensations. Slow rates of cooling could be detected or distinguished. Fast rates appeared to saturate the neuronal and sensory mechanisms.