Non-respiratory Neurons Research Articles

Firing characteristics of swallowing interneurons in the dorsal medulla during physiologically induced swallowing in perfused brainstem preparation in rats

Oropharyngeal swallowing is centrally mediated by a swallowing central pattern generator (Sw-CPG) in the medulla oblongata. The activity of the Sw-CPG depends on the sensory inputs determined by physical and chemical bolus properties. Here we investigate the sensory-motor integration during swallowing arising from different sensory sources. To do so we electrically stimulated the superior laryngeal nerve and we triggered swallowing with oral injections of distilled water or capsaicin solution and extracellularly recorded from swallowing interneurons in arterially perfused brainstem preparations of rats. We recorded the activities of 40 neurons, while monitoring the motor activities of the phrenic, vagal and hypoglossal nerves. Eighteen neurons responded to electrical stimulation of the ipsilateral superior laryngeal nerve, and 6 neurons were excited by oral fluid injection, while 16 non-respiratory neurons did not receive afferent inputs to either electrical or physiological stimuli. The cellular activities displayed by swallowing interneurons during electrical and physiological stimulation of pharyngeal and laryngeal afferent input reveal complex adaptations of the timing of firing patterns and frequencies. The modulation of neuronal activity is likely to contribute to the coordination of efficient bolus transfer during the pharyngeal stage of swallowing.

Cough-related neurons in the nucleus tractus solitarius of decerebrate cats

This study was carried out on decerebrate, paralyzed and artificially ventilated cats to investigate the central regulatory mechanism for cough reflex. Fictive cough was induced by repetitive stimulation of the superior laryngeal nerve (SLN) or the nucleus tractus solitarius (NTS), and characterized by an increased inspiratory discharge in the phrenic nerve (stage 1 of cough; S1C) and large burst discharge in the iliohypogastric nerve (stage 2 of cough; S2C). Membrane potential was recorded from the neurons located in the cough-inducible sites of the NTS. Seven augmenting inspiratory (aug-I), 25 inspiratory-modulated (I-mod) and 16 non-respiratory (non-R) neurons were encountered, all of which showed short-latency (7.5±1.6ms, n=48) waves of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in response to single pulse stimulation of the SLN. Out of these, all 7 aug-I and 12 I-mod neurons depolarized during the S1C and hyperpolarized during the S2C (DH-type response). Three I-mod and five non-R neurons showed membrane hyperpolarization during both stages (HH-type response). Ten I-mod and three non-R neurons displayed membrane depolarization during the S1C and S2C (DD-type response). The remaining eight non-R neurons showed no response during the fictive cough (NN-type response) but a long-lasting EPSP wave to single SLN stimulation. The NTS neurons recorded here were divided into three groups. Group I neurons with the NN-type response may be the second-order relay neurons. Group II neurons with the DD-type response may integrate the tussigenic afferent information and send a gate signal to the cough pattern generator. Group III neurons with either DH-type or HH-type response may constitute the network of cough pattern generation or modulatory circuits recruited during the cough reflex. The present study suggests that Group II neurons may play a gating role in generating the cough reflex.

Silencing by raised extracellular Ca 2+ of pre-Bötzinger complex neurons in newborn rat brainstem slices without change of membrane potential or input resistance

Breathing is controlled by inspiratory pre-Bötzinger complex (preBötC) networks that remain active in transversal brainstem slices from perinatal rodents. In 600 μm thick preBötC slices, inspiratory-related bursting in physiological (3 mM) [K +] is depressed by <1 mM elevation of superfusate [Ca 2+]. Here, we studied underlying cellular mechanisms in whole-cell-recorded neurons of 400 μm thin newborn rat slices with the <200 μm thin preBötC in the middle (“m-preBötC[400]” slices). Extracellular activity in the ventrolateral slice area in 3 mM K + and a most common physiological Ca 2+ range (1–1.2 mM) stopped spontaneously within 2 h (“in vitro apnea”). Contrary, rhythm was stable for >3 h at 6–8 bursts/min in 7 mM K + and 1.2 mM Ca 2+ solution. In non-pacemaker preBötC inspiratory cells and neighboring inspiratory or tonically active neurons, block or frequency depression by >90% of rhythm in the latter solution by 2–3 mM Ca 2+ changed neither resting potential nor input resistance. High Ca 2+ silenced inspiratory neurons and depressed tonic discharge of non-respiratory neurons. However, in both cell types current injection evoked normal action potentials with unchanged threshold potential. The findings show that m-preBötC[400] slices represent a good compromise between long term viability of rhythmogenic preBötC neurons and minimal modulation of these cells by adjacent tissue, but need to be studied in elevated K +. The lack of postsynaptic K + channel-mediated hyperpolarization suggests that saturation of surface charges, presynaptic block of transmission and/or inhibition of postsynaptic burst-promoting conductances such as Ca 2+ activated non-selective cation channels are involved in inspiratory depression by high Ca 2+.

ATP sensitivity of preBötzinger complex neurones in neonatal rat in vitro: mechanism underlying a P2 receptor‐mediated increase in inspiratory frequency

P2 receptor (R) signalling plays an important role in the central ventilatory response to hypoxia. The frequency increase that results from activation of P2Y(1)Rs in the preBötzinger complex (preBötC; putative site of inspiratory rhythm generation) may contribute, but neither the cellular nor ionic mechanism(s) underlying these effects are known. We applied whole-cell recording to rhythmically-active medullary slices from neonatal rat to define, in preBötC neurones, the candidate cellular and ionic mechanisms through which ATP influences rhythm, and tested the hypothesis that putative rhythmogenic preBötC neurones are uniquely sensitive to ATP. ATP (1 mm) evoked inward currents in all non-respiratory neurones and the majority of respiratory neurons, which included inspiratory, expiratory and putative rhythmogenic inspiratory neurones identified by sensitivity to substance P (1 microM) and DAMGO (50 microM) or by voltage-dependent pacemaker-like activity. ATP current densities were similar in all classes of preBötC respiratory neurone. Reversal potentials and input resistance changes for ATP currents in respiratory neurones suggested they resulted from either inhibition of a K(+) channel or activation of a mixed cationic conductance. The P2YR agonist 2MeSADP (1 mm) evoked only the latter type of current in inspiratory and pacemaker-like neurones. In summary, putative rhythmogenic preBötC neurones were sensitive to ATP. However, this sensitivity was not unique; ATP evoked similar currents in all types of preBötC respiratory neurone. The P2Y(1)R-mediated frequency increase is therefore more likely to reflect activation of a mixed cationic conductance in multiple types of preBötC neurone than excitation of one, highly sensitive group.

Reactions and Functional Relationships between Nonrespiratory Neurons in the Medulla Oblongata after Central Application of Penicillin

Changes in impulse activity of nonrespiratory neurons in the medulla oblongata produced by central administration of penicillin were studied in acute experiments on narcotized immobilized rats. The mean firing frequency increased in most neurons. The peaks on histograms for the distribution of interspike intervals were shifted toward shorter intervals and their amplitude increased; the type of distribution was also changed. Tonic activity of neurons was transformed into burst activity. Study of auto- and cross-correlation histograms for neuronal pairs showed that hyperactivation of structures was accompanied by an increase in the degree of synchronization. These changes reflect the appearance of new functional relationships between neurons in the respiratory center. We found that nonrespiratory reticular neurons are involved in the mechanisms of normal and pathological respiratory rhythm generation and serve as a functionally labile component of the neuronal respiratory network.

Reactions and functional relationships between nonrespiratory neurons in the medulla oblongata after central application of penicillin

Reactions and functional relationships between nonrespiratory neurons in the medulla oblongata after central application of penicillin

Intracellular activity of superior laryngeal nerve motoneurons during fictive swallowing in decerebrate rats

We examined the swallowing-related intracellular activity of motoneurons of the superior laryngeal nerve (SLN) in decerebrate, paralyzed and artificially-ventilated rats, to elucidate the neuronal mechanism of the pharyngo-esophageal and laryngo-esophageal coordination during swallowing. The majority of the SLN motoneurons exhibited respiratory rhythm ( n=16; 13 inspiratory, one expiratory and two non-respiratory neurons). During fictive swallowing evoked by electrical stimulation of the SLN, all these motoneurons showed a hyperpolarization–depolarization sequence in their membrane potentials. The hyperpolarization, which was shown to consist of inhibitory postsynaptic potentials, started at the onset of the hypoglossal swallowing burst, lasted during the burst, and was followed by a depolarization at the end of the burst. This hyperpolarization–depolarization pattern implies that the SLN motoneurons may be involved in the ‘inhibitory chain’ within the swallowing pattern generator, which may be cardinal in the sequential activation of different populations of motoneurons innervating the swallowing-related muscles.

Difference between hypoglossal and phrenic activities during lung inflation and swallowing in the rat

We aimed in this study to elucidate the discharge properties and neuronal mechanisms of the dissociation between hypoglossal and phrenic inspiratory activities in decerebrate rats, which had been subjected to neuromuscular blockade and artificially ventilated. The discharge of the hypoglossal nerve and the intracellular activity of hypoglossal motoneurones were monitored during respiration and fictive-swallowing evoked by electrical stimulation of the superior laryngeal nerve, and were compared with the activity of the phrenic nerve. The hypoglossal nerve activity was characterized by its onset preceding the phrenic nerve activity ('pre-I' activity). By manipulating artificial respiration, we could augment the 'pre-I' activity, and could elicit another type of hypoglossal activity decoupled from the phrenic-associated inspiratory bursts ('decoupled' activity). We further scrutinized the correlatives of 'pre-I' and 'decoupled' activities in individual hypoglossal motoneurones. Hypoglossal motoneurones consisted of inspiratory (n = 42), expiratory (n = 18) and non-respiratory (n = 1) neurones and were classified by their swallowing activity into depolarized, hyperpolarized, hyperpolarized-depolarized and unresponsive groups. All of the inspiratory neurones were depolarized in accordance with the 'pre-I' and 'decoupled' activities, and all of the expiratory neurones were hyperpolarized during these activities. Fictive swallowing, which was characterized by its frequent emergence just after the phrenic inspiratory activity, was also evoked just after the 'decoupled' hypoglossal activity, suggesting that this activity may have similar effects on swallowing as the 'overt' inspiratory activity. Such a coupling between 'decoupled' and swallowing activities was also revealed in each motoneurone. These findings suggest that the 'pre-I' and 'decoupled' activities may reflect some internal inspiratory activity of the respiratory centre and that hypoglossal motoneurones may be driven by a distinct group of premotor neurones that possibly play a role in the coordination of respiration and swallowing.

Swallowing-related activities of respiratory and non-respiratory neurons in the nucleus of solitary tract in the rat.

Swallowing-related activity was examined in respiratory (n = 60) and non-respiratory (n = 82) neurons that were located in and around the nucleus of the solitary tract (NTS) in decerebrated, neuromuscularly blocked and artificially ventilated rats. Neurons that were orthodromically activated by electrical stimulation of the superior laryngeal nerve (SLN) were identified, and fictive swallowing was evoked by SLN stimulation. The pharyngeal phase of swallowing was monitored by hypoglossal nerve activity. Two types of non-respiratory neurons with swallowing-related bursts were identified: 'early' swallowing neurons (n = 24) fired during periods of hypoglossal bursts, and 'late' swallowing neurons (n = 8) fired after the end of hypoglossal bursts. The remaining non-respiratory neurons were either suppressed (n = 21) or showed no change in activity (n = 29) during swallowing. On the other hand, respiratory neurons with SLN inputs included 56 inspiratory and four expiratory neurons. Inspiratory neurons were classified into two major types: a group of neurons discharged simultaneously with hypoglossal bursts (type 1 neurons, n = 19), while others were silent during bursts but were active during inter-hypoglossal bursts when swallowing was provoked repetitively (type 2 neurons, n = 34). Three of the expiratory neurons fired during hypoglossal bursts. Many of the swallowing-related non-respiratory neurons and the majority of the inspiratory neurons received presumed monosynaptic inputs from the SLN. Details of the distribution and firing patterns of these NTS neurons, which have been revealed for the first time in a fictive swallowing preparation in the rat, suggest their participation in the initiation, pattern formation and mutual inhibition between swallowing and respiration.

Swallowing-related activities of respiratory and non-respiratory neurons in the nucleus of solitary tract in the rat

Swallowing-related activity was examined in respiratory (n= 60) and non-respiratory (n= 82) neurons that were located in and around the nucleus of the solitary tract (NTS) in decerebrated, neuromuscularly blocked and artificially ventilated rats. Neurons that were orthodromically activated by electrical stimulation of the superior laryngeal nerve (SLN) were identified, and fictive swallowing was evoked by SLN stimulation. The pharyngeal phase of swallowing was monitored by hypoglossal nerve activity. Two types of non-respiratory neurons with swallowing-related bursts were identified: ‘early’ swallowing neurons (n= 24) fired during periods of hypoglossal bursts, and ‘late’ swallowing neurons (n= 8) fired after the end of hypoglossal bursts. The remaining non-respiratory neurons were either suppressed (n= 21) or showed no change in activity (n= 29) during swallowing. On the other hand, respiratory neurons with SLN inputs included 56 inspiratory and four expiratory neurons. Inspiratory neurons were classified into two major types: a group of neurons discharged simultaneously with hypoglossal bursts (type 1 neurons, n= 19), while others were silent during bursts but were active during inter-hypoglossal bursts when swallowing was provoked repetitively (type 2 neurons, n= 34). Three of the expiratory neurons fired during hypoglossal bursts. Many of the swallowing-related non-respiratory neurons and the majority of the inspiratory neurons received presumed monosynaptic inputs from the SLN. Details of the distribution and firing patterns of these NTS neurons, which have been revealed for the first time in a fictive swallowing preparation in the rat, suggest their participation in the initiation, pattern formation and mutual inhibition between swallowing and respiration.

Chemosensitivity of non-respiratory rat CNS neurons in tissue culture

Neurons from many brainstem nuclei involved in respiratory control increase their firing rate in response to acidosis in vitro, suggesting that they are central chemoreceptors. This property has been considered to be either unique to neurons involved in respiratory control, or at least very unusual for non-respiratory neurons. However, recordings of intrinsic pH responses of neurons have not been made from enough non-respiratory regions of the CNS to be certain this assumption is true. Here, we have quantified changes in firing rate of neurons cultured from the hippocampus ( n=43), neocortex ( n=33), and cerebellum ( n=29) in response to changes in CO 2 between 3% and 9% (pH≈7.6–7.2) after blockade of glutamatergic and GABAergic transmission. The responses of neurons from these three regions were similar, with a subset of neurons (12% of the total 105) inhibited by acidosis, decreasing their firing rate to a mean of 70% of control in response to a decrease in pH of 0.2. Some neurons (5% of total) were stimulated by acidosis, with an increase in firing rate to a mean of 175% of control in response to a decrease in pH of 0.2. We previously quantified chemosensitivity of neurons from the medullary raphe using the same methods [W. Wang, J.H. Pizzonia, G.B. Richerson, Chemosensitivity of rat medullary raphe neurones in primary tissue culture, J. Physiol., 511 (1998) 433–450]. Compared to these non-respiratory neurons, more raphe neurons were stimulated by acidosis (22%), and the average response was greater (to 300% of control) in response to the same stimulus. Thus, over a physiologically relevant pH range, stimulation by acidosis occurs in a significant percentage of neurons not involved in respiratory chemoreception. However, the degree of chemosensitivity of these neurons was less than medullary raphe neurons under the same conditions. Chemosensitivity is not an all-or-none neuronal property, and the degree of chemosensitivity may be relevant to the role neurons play in sensing pH in vivo.

Synaptic inhibition in the isolated respiratory network of neonatal rats.

Gramicidin-perforated patch-clamp recording revealed phasic Cl(-)-mediated hyperpolarizations in respiratory neurons of the brainstem-spinal cord preparation from newborn rats. The in vitro respiratory rhythm persisted after block of gamma-aminobutyric acid (GABA), i.e. GABAA, receptor-mediated inhibitory postsynaptic potentials (IPSPs) with bicuculline and/or glycinergic IPSPs with strychnine. In one class of expiratory neurons, bicuculline unmasked inspiration-related excitatory postsynaptic potentials (EPSPs), leading to spike discharge. Bicuculline also blocked hyperpolarizations and respiratory arrest due to bath-applied muscimol, whereas strychnine antagonized similar responses to glycine. The reversal potential of respiration-related IPSPs and responses to GABA, muscimol or glycine was not affected by CO2/HCO3(-)-free solutions, but shifted from about -65 mV to values more positive than -20 mV upon dialysis of the cells with 144 instead of 4 mM Cl-. Impairment of GABA uptake with nipecotic acid or glycine uptake with sarcosine evoked a bicuculline- or strychnine-sensitive decrease of respiratory frequency which could lead to respiratory arrest. Also, the GABAB receptor agonist baclofen led to reversible suppression of respiratory rhythm. This in vitro apnoea was accompanied by a K+ channel-mediated hyperpolarization (reversal potential -88 mV) of tonic cells, whereas membrane potential of neighbouring respiratory neurons remained almost unaffected. Both baclofen-induced hyperpolarization and respiratory depression were antagonised by 2-OH-saclofen, which did not affect respiration-related IPSPs per se. The results show that synaptic inhibition is not essential for rhythmogenesis in the isolated neonatal respiratory network, although (endogenous) GABA and glycine have a strong modulatory action. Hyperpolarizing IPSPs mediated by GABAA and glycine receptors provide a characteristic pattern of membrane potential oscillations in respiratory neurons, whereas GABAB receptors rather appear to be a feature of non-respiratory neurons, possibly providing excitatory drive to the network.

Axonal projections from the pontine parabrachial-Kölliker-Fuse nuclei to the Bötzinger complex as revealed by antidromic stimulation in cats.

The pontine parabrachial and Kölliker-Fuse nuclear complex (NPB-KF) has been assumed to be the anatomical location of the pneumotaxic center (11). It contains high density of respiratory neurons with various discharge patterns (3, 6). Destruction or electrical stimulation of this area is known to produce profound changes in the respiratory rhythm (5, 24, 25). It is suggested that the NPB-KF exerts its effects by specifically modulating the activity of the medullary inspiratory ‘off-switch’ mechanism, which terminates inspiration and ensures the phase transition from inspiration to expiration (8, 9). However, axonal projections from the NPB-KF to the medullary structures specifically involved in the inspiratory ‘off-switch’ effects have not been well delineated. Previous studies by us demonstrated that the nucleus raphe magnus, a structure involved in the inspiratory ‘off-switch’, received strong axonal projections from the NPB-KF area (1, 21, 22). Another possible neuron group which may transmit the function of the NPB-KF is the Bötzinger complex (Böte). The Böt. c. is known as a group of expiratory neurons in the vicinity of the retrofacial nucleus (14, 19). Most of those neurons have an augmenting firing pattern and widespread inhibitory connections to the medullary inspiratory premotor neurons (10, 12, 18). Recent studies by Smith et al. (20) and us (23) with the retrograde WGA-HRP tracing method revealed that the Böt. c. received strong projections from the lateral NPB and the KF. These studies suggest that these projections are composed of axons from the pontine respiratory and/or non-respiratory neurons which would modulate the activities of expiratory neurons in the Böt. c.KeywordsAxonal ProjectionNucleus ParabrachialisRespiratory NeuronAxonal ArborizationVentral Respiratory GroupThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Role of respiratory and non-respiratory neurones in the region of the NTS in the elaboration of the sneeze reflex in cat

Extracellular recordings were made in the dorsal respiratory group (DRG) and adjacent reticular formation following single-shock stimulation of the anterior ethmoidal nerve (AEN) and during sneeze evoked by repetitive stimulation of the AEN in nembutal-anaesthetized, curarized and ventilated cats. These neurones were characterised according to (i) their activity during the respiratory cycle (as inspiratory augmenting or decrementing (I Aug or I Dec), expiratory augmenting or decrementing (E Aug or E Dec), silent or tonic), and (ii) their axonal projection (bulbospinal or non-bulbospinal–non-vagal (BS or NBS–NV)). Following single-shock stimulation of the AEN, most of the inspiratory neurones were transiently inhibited, whereas E Aug neurones were activated and E Dec neurones were activated and then inhibited. Silent neurones responded with a multispike or a paucispike pattern. Following repetitive stimulation of the AEN and during the resulting sneeze reflex, I Aug neurones increased their activity in parallel with the phrenic activity, I Dec neurones fired at the onset and at the end of the inspiration, E Dec and some silent neurones fired either during the compressive phase or after the expulsive phase, whereas E Aug and some silent neurones fired during the expulsive phase. We conclude that sneeze involves a reconfiguration of the central respiratory drive which uses, at least partly, the respiratory network to trigger a non-ventilatory defensive motor act.

Descending pathway from the central pattern generator of vomiting.

The central pattern generator (CPG) for vomiting has been postulated to consist of non-respiratory neurons in the reticular area dorsomedial to the retrofacial nucleus. CPG neurons are known to produce vomiting activity patterns similar to respiratory spinal motoneurons and premotoneurons in the caudal part of the ventral respiratory group (cVRG). This study was performed to reveal direct connections between CPG neurons and cVRG neurons in dogs. Twenty-seven non-respiratory neurons were identified as CPG neurons based on their responses to vagal stimulation and their firing patterns of vomiting. Nine of these 27 neurons antidromically responded to cVRG stimulation. These results suggest that the CPG directly drives respiratory premotor neurons in the cVRG to produce vomiting motions.

Neuronal gagging activity patterns may be generated by neurons in the reticular area dorsomedial to the retrofacial nucleus in dogs.

Expulsion is induced when hypercapnea and hypoxia develop during retching, or when the oropharyngeal mucosa is irritated (the gag reflex). The central pattern generator (CPG) for expulsion has been suggested to coexist with the CPG for retching in the reticular area dorsomedial to the retrofacial nucleus, which may correspond to the Botzinger complex (BOT). However, its participation in gagging induced by oropharyngeal irritation is unclear. To elucidate such participation, the firing patterns of BOT neurons were observed during gagging induced by stimulation of superior laryngeal afferents in decerebrate, paralyzed dogs. Only 23% of inspiratory and 34% of expiratory BOT neurons increased their firing in response to stimulation of the superior laryngeal nerve. In contrast, 75% of nonrespiratory BOT neurons showed enhanced firing with this stimulation. During gagging, each nonrespiratory, inspiratory, and expiratory BOT neuron fired with the same pattern that they exhibited during expulsion caused by changes in blood gases. These firing patterns could be classified into five types and are thought to be appropriate for generating neuronal gagging activity. These results suggest that the CPG for expulsion in the BOT produces gagging when it is activated by oropharyngolaryngeal afferents.

Changes in outflow to respiratory pump muscles produced by natural vestibular stimulation.

1. Activity was recorded from abdominal (expiratory) and phrenic (inspiratory) nerves during natural vestibular stimulation in multiple vertical planes and the horizontal plane in decerebrate cats. Vestibular stimulation was produced by rotating the head in animals whose upper cervical dorsal roots were transected to remove inputs from neck receptors; the upper airway and carotid sinus were denervated, and the vagus nerves were transected to assure that the head rotations did not elicit visceral or pulmonary inputs. 2. The plane of head rotation that produced maximal modulation of respiratory nerve activity (response vector orientation) was measured at one or more frequencies between 0.05 and 0.5 Hz. The dynamics of the response were then studied with sinusoidal (0.05-2 Hz) stimuli aligned with this orientation. In some animals, sinusoidal horizontal rotations of the head at 0.5 and 1 Hz or static head tilts in the pitch and roll planes were also delivered. 3. Typically, maximal modulation of abdominal nerve outflow was elicited by head rotations in a plane near pitch; nose-up rotations produced increased outflow, and nose-down rotations reduced nerve discharges. The gains of the responses (relative to stimulus position) remained relatively constant across stimulus frequencies, and the phases were consistently near stimulus position, like regularly firing otolith afferents. Static nose-up tilt produced elevated abdominal nerve activity throughout the stimulus period, providing further evidence that pitch-sensitive otolith receptors contribute to the response. Horizontal head rotations had little influence on abdominal nerve discharges. 4. The abdominal nerve responses to head rotation were abolished by chemical or aspiration lesions of the medial and inferior vestibular nuclei, which is concordant with the responses resulting from activation of vestibular receptors. Transections of axons arising from bulbospinal neurons in the ventral respiratory group, which are known to be the predominant source of expiratory signals to the spinal cord, reduced but did not abolish the vestibuloabdominal reflex. Thus it is likely that nonrespiratory neurons also participate in generating this response. 5. Nose-up pitch of the head; and in particular large (50 degrees) static tilts, produced small increases in phrenic nerve activity. Ear-down tilt and horizontal rotation of the head produced no responses in the phrenic nerve. 6. The existence of vestibular inputs to some respiratory motoneurons suggests that the vestibular system has influences on muscles in addition to those typically considered to have antigravity roles, and participates globally in adjusting muscle activity during movement and changes in posture.

Inspiratory drive and phase duration during carotid chemoreceptor stimulation in the cat: medullary neurone correlations.

1. This study addressed the hypothesis that there is a parallel processing of input from carotid chemoreceptors to brainstem neurones involved in inspiratory phase timing and control of inspiratory motor output amplitude. Data were from fifteen anaesthetized, bilaterally vagotomized, paralysed, artificially ventilated cats. Carotid chemoreceptors were stimulated by close arterial injection of 200 microliters of CO2-saturated saline solution. 2. Planar arrays of tungsten microelectrodes were used to monitor simultaneously up to twenty-two neurones in the nucleus tractus solitarii (NTS) and ventral respiratory group (VRG). Spike trains were analysed with two statistical tests of respiratory modulation, cycle-triggered histograms, peristimulus-time histograms, cumulative sum histograms and cross-correlograms. 3. In NTS, 16 of 26 neurones with respiratory and 12 of 27 without respiratory modulation changed firing rate during carotid chemoreceptor stimulation. In the VRG 72 of 112 respiratory and 14 of 48 non-respiratory neurones changed firing rate during stimulation. 4. The spike trains of 85 of 1276 pairs (6.7%) of cells exhibited short time scale correlations indicative of paucisynaptic interactions. Ten pairs of neurones were each composed of a rostral VRG phasic inspiratory neurone that responded to carotid chemoreceptor stimulation with a decline in firing rate and a caudal VRG phasic inspiratory neurone that increased its firing rate. Cross-correlograms from two of the pairs had features consistent with excitation of the caudal neurones by the rostral cells. A decrease in the duration of activity of the rostral VRG neurones was paralleled by the decrease in inspiratory time of phrenic nerve activity. Caudal VRG inspiratory neurones increased their activity as phrenic amplitude increased. Spike-triggered averages of all four neurones indicated post-spike facilitation of phrenic motoneurones. 5. The results support the hypothesis that unilateral stimulation of carotid chemoreceptors results in parallel actions. (a) Inhibition of rostral VRG I-Driver neurones decreases inspiratory duration. (b) Concurrent excitation of premotor VRG and dorsal respiratory group inspiratory neurones increases inspiratory drive to phrenic motoneurones. Other data suggest that responsive ipsilateral neurones act to regulate contralateral neurones.

Descending pathways necessary for vestibular influences on sympathetic and inspiratory outflow.

The objective of this study was to determine which brain stem regions that have projections to sympathetic preganglionic neurons or phrenic motoneurons ae necessary for vestibulosympathetic or vestibulorespiratory responses in decerebrate cats. Bilateral kainic acid injections into the rostral ventrolateral medulla abolished splanchnic nerve responses to electrical stimulation of the vestibular nerve, suggesting that this region is critical for the production of vestibulosympathetic responses. In contrast, injections into the caudal medullary raphe nuclei had no apparent effect on the responses. Neither the dorsal nor the ventral respiratory group appears to be necessary for mediating vestibular influences on the phrenic nerve, suggesting that nonrespiratory neurons (such as vestibulospinal neurons) may be important for producing vestibulorespiratory responses.

Pontine respiratory neurons in anesthetized cats

The pontine respiratory neurons (PRG) in the ‘pneumotaxic centre’ have been hypothesized to contribute to phase-switching of neural respiratory activity, especially in terminating inspiration. To define the neural elements involved in phase-switching, we recorded respiratory neurons extra- and intracellularly in anesthetized cats with an intact central nervous system. In total, 54 neurons were recorded: 49 neurons with activity modulated by central respiratory rhythm (20 inspiratory, 17 postinspiratory and 12 expiratory) and 5 neurons with activity correlated to tracheal pressure. The recorded neurons were clustered in dorsolateral pontine tegmentum within the Ko¨lliker-Fuse (KF) subnucleus of the parabrachial nuclei. Stable intracellular membrane potential was recorded in 11 of the 49 respiratory neurons (8 postinspiratory, 1 early inspiratory and 2 inspiratory). During continuous injection of chloride ions( n = 6), synaptic noise increased and IPSPs reversed, including a wave of IPSPs during stage-2 expiration in postinspiratory neurons. Further, relative input resistance varied through the respiratory cycle such that the least input resistance occurred during the neuron's( n = 5) quiescent period. No IPSPs nor EPSPs were evoked in pontine respiratory neurons by vagal stimulation. In conclusion, various types of respiratory neurons were recorded in the KF nucleus. Prominent excitatory and inhibitory postsynaptic activities were similar to those described for medullary neurons. These pontine respiratory neurons do not appear to receive a strong afferent input from the vagus. Rather, vagal afferent inputs seem to be directed towards non-respiratory neurons that are located more medially in the dorsal pons.