Caudal Ventral Respiratory Group Research Articles

Depressant effects on inspiratory and expiratory activity produced by chemical activation of Bötzinger complex neurons in the rabbit

The respiratory role of the Bötzinger complex (Böt. c.) was investigated in α-chloralose-urethane or pentobarbitone anesthetized rabbits by means of microinjections of dl-homocysteic acid (DLH). The animals were either spontaneously breathing or vagotomized. paralysed and artificially ventilated. Both phrenic and abdominal activities were monitored: extracellular recordings from medullary respiration-related neurons were performed. Unilateral microinjections (5–30 nl) of DLH (160 mM) into the Böt. c., at sites where intense expiratory activity with an augmenting discharge pattern was encountered, provoked mild or moderate depressant effects on inspiratory activity characterized by decreases in frequency as well as in peak amplitude and rate of rise of phrenic nerve discharge. Stronger depressant effects up to complete apnea were consistently obtained in response to bilateral microinjections. Concomitant depressant effects on the activity of both expiratory motoneurons and expiration-related (ER) neurons of the caudal ventral respiratory group (cVRG) were observed. At variance with previous findings in the cat, the results indicate that chemical activation of Böt. c. augmenting ER neurons may exert inhibitory influences not only on inspiratory activity, but also on cVRG ER neurons and, hence, on expiratory motoneurons. The functional role of the Böt. c. in the control of respiration deserves further investigations; present findings suggest that the rabbit may profitably be used for such a purpose.

Simultaneous optical recording of calcium and voltage transients in the organotypic hippocampal cultures in rat

Abdominal musculature participates in generating a large number of behaviors and protective reflexes, although each abdominal muscle is frequently activated differentially during particular motor responses. For example, rectus abdominis has been reported to play less of a role in respiration than other abdominal muscles, such as transversus abdominis. In the present study, the inputs to transversus abdominis and rectus abdominis motoneurons were determined and compared using the transneuronal transport of two recombinant isogenic strains of pseudorabies virus. After a 5-day post-inoculation period, infected presumed motoneurons were observed principally in cord levels T10–T15 ipsilateral to the injections. The injection of a monosynaptic tracer, β-cholera toxin, into transversus abdominis confirmed the distribution of motoneurons innervating this muscle. In the brainstem, neurons transneuronally infected following injection of pseudorabies virus into rectus abdominis or transversus abdominis were located in the same regions, which included the medial medullary reticular formation, the medullary raphe nuclei, and nucleus retroambiguus (the expiration region of the caudal ventral respiratory group). Double-labeled cells providing inputs to both rectus and transversus motoneurons were present in both the medial medullary reticular formation and nucleus retroambiguus. These data show that the medial medullary reticular formation contains neurons influencing the activity of multiple abdominal muscles, and support our hypothesis that this region globally affects the excitability of motoneurons involved in respiration.

Functional role of ventral respiratory group expiratory neurons during vocalization

The activities of expiratory neurons of the caudal ventral respiratory group (cVRG) ( n = 31) were recorded extracelluarly during vocalization in unanesthetized, decerebrate cats. Vocalization was induced by electrical stimulation (0.2 ms, 20–80 μA, 100 Hz, lasting for 2–5 s) of the periaqueductal gray (PAG). The firing rates of more than two-thirds of the neurons ( 24 31 ) increased during periods of vocalization induced by stimulation of the PAG, with an increase in abdominal muscle activities. The axons of most of these neurons ( 19 24 ) projected to the contralateral lumbar spinal cord, and one-third of the bulbospinal neurons ( 6 19 ) were orthodromically activated by stimulation of the PAG. Even after sectioning of the axons of bulbospinal cVRG neurons by midsagittal lesion between the obex and the C 1 spinal cord, stimulation of the PAG still induced adduction of the vocal cords and vocalization. However, activities of abdominal muscles during vocalization were abolished. These results indicate that the efferent signals for vocalization from the PAG may be relayed at the cVRG neurons and converted into adequate activation of these neurons, contributing to the activation of the abdominal muscles for vocalization.

Role of ventral respiratory group bulbospinal expiratory neurons in vestibular-respiratory reflexes.

1. Activation of the vestibular system produces reflex modulation of expiratory muscle activity. The purpose of the present study was to investigate the possible role of bulbospinal expiratory (E) neurons located in the caudal ventral respiratory group (VRG) in mediating vestibulo-respiratory reflexes. Experiments were carried out in decerebrated, paralyzed, and artificially ventilated cats. 2. Electrical stimulation of the vestibular nerve (VN), using short trains of current pulses, elicited bilateral reflex responses on abdominal muscle nerves (ABDNs). This response was not affected by lesions of the cochlear nuclei made by kainic acid injections. The ABDN response typically consisted of a combination of short-latency excitation and long-latency inhibition on the ipsilateral side and, in contrast, a combination of short-latency inhibition and long-latency excitation on the contralateral side. 3. Extracellular recordings were made from 43 caudal VRG bulbospinal E neurons that were activated antidromically from the contralateral upper lumbar spinal cord. More than 80% of these neurons responded to either ipsi- and/or contralateral VN stimulation. The neuronal response consisted of either a combination of excitation and inhibition or only inhibition. The majority of neurons had response patterns appropriate to contribute to the response observed on the contralateral ABDN; however, the latency of the VRG E neuron response was too long to initiate the ABDN response. 4. To further evaluate the contribution of caudal VRG E neurons to the vestibulo-abdominal reflex, ABDN responses were compared before and after sectioning the axons of caudal VRG bulbospinal E neurons where they cross the midline between the obex and first cervical spinal segment. These midsagittal lesions abolished expiratory modulation of ABDN discharge. The lesions also decreased the amplitude of the vestibular-evoked ABDN response but could not abolish the response. The postlesion amplitude was decreased on average to approximately 70% of prelesion values. 5. In conclusion, although the present results indicate that the majority of caudal VRG bulbospinal E neurons respond appropriately to contribute to the vestibulo-abdominal reflex, the reflex largely is unaffected by the removal of caudal VRG E input. The additional descending inputs that are important for mediating the reflex remain to be investigated and may include vestibulospinal and/or reticulospinal tracts.

High-frequency oscillations in membrane potentials of medullary inspiratory and expiratory neurons (including laryngeal motoneurons).

1. In midcollicular decerebrate, unanesthetized, paralyzed cats ventilated with a cycle-triggered pump system, the properties of high-frequency oscillations (HFOs, 50-100 Hz) in membrane potentials (MPs) of medullary inspiratory (I) and expiratory (E) cells were studied. Simultaneous recordings were taken from bilateral phrenic and recurrent laryngeal (RL) nerves and from cells in the intermediate ventral respiratory group (intVRG, 0-1 mm rostral to the obex) or the caudal ventral respiratory group (cVRG, 2-4 mm caudal to the obex). 2. Spectral coherence analyses were used to detect the presence of HFOs during I in I and E cell MPs. Cross-correlation histograms (CCHs) between the cell and phrenic signals were used to ascertain cell-nerve HFO phase relations and to identify cells as RL motoneurons. Of the 103 cells that had significant HFOs (cell-phrenic coherences > or = 0.1), measurable HFO peak lags in the CCH were seen in 53 cells: 1) RL cells (9 I cells and 7 E cells); and 2) other types of cell (8 intVRG I cells, 18 intVRG E cells, and 11 cVRG E cells). These cells had high HFO correlations; the cell-phrenic coherence range was 0.35-0.94, with a mean HFO frequency of 58 Hz. 3. The cell-phrenic HFO lag (in ms) was measured in the CCH as the lag of the primary peak (peak located nearest to 0 lag). The phase lag was defined as (lag of primary peak in ms)/(HFO period in ms). The phase lags differed markedly between two subsets of cells: 1) RL I cells had HFO depolarization peaks that lagged the phrenic HFO peaks (average cell-phrenic phase lag = -0.18); and 2) the non-RL cells, regardless of location (intVRG or cVRG) and type (I or E), had HFO depolarization peaks leading (preceding) the phrenic HFO peaks (average cell-phrenic phase lag = 0.28). In addition, the cVRG E cells had significantly shorter cell-phrenic phase lags than the intVRG E cells (0.23 vs. 0.31, respectively). 4. These lags can be compared with the (I unit)-phrenic phase lags (average approximately 0.3) found in earlier extracellular studies. 1) There is a transmission delay of about one half HFO cycle from excitatory I cells to RL I cells. 2) Because a depolarization peak in the MP of an E cell corresponds to the start of a hyperpolarizing wave, the excitatory bulbospinal pathways from I cells have transmission times comparable with those of the inhibitory intramedullary pathways from I cells to E cells. 5. These results indicate that study of HFO phase relations can furnish useful information on functional connectivity of medullary respiratory neurons during the I phase.

Thyrotropin-releasing hormone immunoreactive boutons form close appositions with medullary expiratory neurons in the rat

The aim of the present study was to assess the size of the input from TRH immunoreactive varicosities to medullary respiratory neurons in the Bötzinger complex and caudal ventral respiratory group. Neurobiotin was intracellularly injected into seven neurons in the Bötzinger complex, between 0.4 and 0.9 mm caudal to the facial nucleus. Five of the seven Bötzinger neurons had extensive local axonal projections, with bouton-like varicosities clustered predominantly between their somata and the nucleus ambiguus. Seven neurons in the caudal ventral respiratory group, located between 1.6 and 2.4 mm caudal to the facial nucleus, were also labelled. All but one caudal respiratory neurons had no, or very few, medullary collaterals. TRH immunoreactive fibres were seen in many medullary nuclei, including the ventral reticular formation. Bötzinger neurons were closely apposed by an average of 29TRH immunoreactive boutons/neuron (mean .D., n = 7). In contrast, caudal ventral respiratory group neurons were apposed by only 5TRH immunoreactive boutons/neuron ( n = 7). Bötzinger neurons form many intramedullary and bulbospinal inhibitory connections with premotoneurons and motoneurons that are important in the timing, amplitude and shape, of respiratory activity. Our findings suggest a role for endogenous TRH-containing neurons in modulating the activity of inhibitory Bötzinger neurons and neurons in the caudal ventral respiratory group. The significance of the apparent difference in size of this input remains to be determined.

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.

Multifunctional ventral respiratory group: Bulbospinal expiratory neurons play a role in pudendal discharge during vomiting

Pudendal motoneurons are activated in phasic bursts during the retching and expulsion phases of vomiting. The resulting contraction of the anal and urethral sphincters serves to maintain continence during the large increase in abdominal pressure that occurs during vomiting. We evaluated the contribution of bulbospinal expiratory neurons located in the portion of the ventral respiratory group (VRG) caudal to the obex (nucleus retroambigualis) to the control of pudendal motoneurons during fictive vomiting in decerebrate, paralyzed cats. Pudendal nerve discharge is abolished by cutting the axons of caudal VRG expiratory neurons as they cross the midline between the obex and C1 before descending in the spinal cord. All caudal VRG expiratory neurons that were antidromically activated from the sacral spinal cord, where the pudendal motor pool (nucleus of Onuf) is located, discharged strongly during the end of the expulsion phase of vomiting. However, only a small proportion of these neurons was active in phase with pudendal discharge during the retching phase. The apparent involvement of caudal VRG expiratory neurons in the control of pudendal motoneurons during vomiting is another example of the multifunctional role that can be played by respiratory-related neurons in the mammalian nervous system.

Brain stem projections by axonal collaterals to the rostral and caudal ventral respiratory group in the rat

The location of neurons projecting by axonal collaterals to the rostral and caudal ventral respiratory group (VRG) regions was determined after discrete injections of Fast blue and Diamidino yellow into the physiologically identified rostral inspiratory VRG and the caudal expiratory VRG areas, respectively. In contrast with single fluorochrome labeled neurons found throughout the rostro-caudal extent of the medulla and pons (in a variety of areas known to have cardiorespiratory function), double-labeled neurons were located in discrete pontomedullary regions. The largest number of the double-labeled neurons was counted within the peripheral facial area, lateral paragigantocellular nucleus, and the VRG region, ipsi- and contralaterally to the injected side. Only a few double-labeled neurons were found within the ventrolateral and intermediate subnuclei of the solitary tract, medial parabrachial, and Kölliker-Fuse nuclei. The possible physiological implications of this neuronal network have also been emphasized.

Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters

Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters

Interaction between chemoreceptor and stretch receptor inputs at medullary respiratory neurons

The interaction between afferent inputs from carotid body chemoreceptors (CCRs) and from slowly adapting pulmonary stretch receptors (PSRs) on the discharge patterns of medullary inspiratory (I) and expiratory (E) neurons was characterized in thiopental sodium-anesthetized, paralyzed, ventilated dogs. A cycle-triggered ventilator was used to produce control and test pulmonary afferent input patterns. The CCRs were stimulated by phase-synchronized bolus injections of CO2-saturated saline into the common carotid arteries. Only those neurons whose discharge time course was altered by both inflation and CCR activation were studied. The dorsal respiratory group (DRG) I inflation-insensitive neurons were also included. Cycle-triggered histograms of unit activity were obtained for the neuronal responses to inflation, CO2 bolus, and their combination, as well as for the spontaneous control condition. Linearity of the interaction was tested by comparing the sum of the net individual responses to the net response of the combined afferent inputs. The results suggest that a linear (additive) interaction between CCR and PSR inputs exists for the DRG I inflation-sensitive neurons, the ventral respiratory group (VRG) I decrementing, and caudal VRG E augmenting neurons, while a nonadditive interaction exists for caudal VRG E decrementing bulbospinal neurons. The implications of these findings are discussed.

Chemical activation of caudal medullary expiratory neurones alters the pattern of breathing in the cat.

1. The purpose of this work was to ascertain whether the activation of caudal expiratory neurones located in the caudal part of the ventral respiratory group (VRG) may affect the pattern of breathing via medullary axon collaterals. 2. We used microinjections of DL-homocysteic acid (DLH) to activate this population of neurones in pentobarbitone-anaesthetized, vagotomized, paralysed and artificially ventilated cats. Both phrenic and abdominal nerve activities were monitored; extracellular recordings from medullary and upper cervical cord respiratory neurones were performed. 3. DLH (160 mM) microinjected (10-30 nl for a total of 1.6-4.8 nmol) into the caudal VRG, into sites where expiratory activity was encountered, provoked an intense and sustained activation of the expiratory motor output associated with a corresponding period of silence in phrenic nerve activity. During the progressive decline of the activation of abdominal motoneurones, rhythmic inspiratory activity resumed, displaying a decrease in frequency and a marked reduction or the complete suppression of postinspiratory activity as its most consistent features. 4. Medullary and upper cervical cord inspiratory neurones exhibited inhibitory responses consistent with those observed in phrenic nerve activity, while expiratory neurones in the caudal VRG on the side contralateral to the injection showed excitation patterns similar to those of abdominal motoneurones. On the other hand, in correspondence to expiratory motor output activation, expiratory neurones of the Bötzinger complex displayed tonic discharges whose intensity was markedly lower than the peak level of control breaths. 5. Bilateral lignocaine blockades of neural transmission at C2-C3 affecting the expiratory and, to a varying extent, the inspiratory bulbospinal pathways as well as spinal cord transections at C2-C3 or C1-C2, did not suppress the inhibitory effect on inspiratory neurones of either the ipsi- or contralateral VRG in response to DLH microinjections into the caudal VRG. 6. The results show that neurones within the column of caudal VRG expiratory neurones promote inhibitory effects on phrenic nerve activity and resetting of the respiratory rhythm. We suggest that these effects are mediated by medullary bulbospinal expiratory neurones, which may, therefore, have a function in the control of breathing through medullary axon collaterals.

Synaptic interaction between medullary respiratory neurones during apneusis induced by NMDA-receptor blockade in cat.

1. Termination of inspiration is an essential component of respiratory rhythm generation and its perturbation can result in apneusis, i.e. significant prolongation of mechanisms, we studied the postsynaptic events in respiratory neurones during apneustic respiratory periods, and compared them to normal respiratory cycles. 2. Experiments were performed in pentobarbitone-anaesthetized, paralysed, thoracotomized cats ventilated with a constant volume or a cycle-triggered constant pressure pump. Apneusis, separated by normal cycles, was induced as follows: the animal was ventilated by a cycle-triggered pump that normally inflated the lungs during the inspiratory burst of phrenic nerve discharge. The NMDA-receptor blocker MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-iminemaleate] (0.3-0.7 mg/kg) was administered intravenously, and, for designated breaths, inflation of the lungs was withheld during neural inspiration. 3. Membrane potential trajectories of forty-one late expiratory (E-2) and eight postinspiratory (PI) neurones of the caudal ventral respiratory group were analysed before and/or after MK-801 administration, during normal and apneustic periods. 4. Before MK-801 administration, withholding lung inflation caused modest (10-20%) lengthening of the inspiratory period; after MK-801 administration, withholding inflation caused apneusis. Provided that the lungs were inflated during the inspiratory phase, the temporal pattern of phrenic nerve, recurrent laryngeal nerve and membrane potential trajectories of E-2 and PI neurones were not significantly altered by MK-801. Apneusis following NMDA-receptor blockade produced consistent changes in the synaptic activation patterns of E-2 neurones. In particular, the slow late inspiratory-related depolarization pattern of E-2 neurones was consistently retarded during apneustic inspiratory phases when compared to normal inspiratory phases. This was due to continuation of Cl(-)-mediated synaptic inhibition of E-2 neurones. Superior laryngeal nerve stimulation stopped apneusis and sustained membrane hyperpolarization of E-2 neurones similar to lung inflation. 5. During the plateau phase of apneusis, correlated 10-20 Hz oscillations could be observed in the integrated phrenic and recurrent laryngeal nerve activities as well as in the membrane potential of E-2 neurones. 6. We conclude that: (i) the prolonged inhibition of E-2 neurones during apneusis is indicative of the process responsible for the prolongation of the inspiratory phase.(ABSTRACT TRUNCATED AT 400 WORDS)

Lower lumbar branching of caudal medullary expiratory neurons of the cat

Extracellular spike activities of medullary expiratory (E) neurons in the caudal ventral respiratory group were recorded in cats anesthetized with sodium pentobarbital. The majority of E neurons extended their axons in the lower lumbar or the sacral segments and distributed collaterals in L5–L7. These results suggest that E neurons are involved not only in respiratory activities but also in the respiratory modulated motor activities of the lower lumbar segments.

Expiration-related neurons in the caudal ventral respiratory group of the cat: influences of the activation of Bo¨tzinger complex neurons

The functional role of Bo¨tzinger complex;(Bo¨t. c.) projections to the expiration-related (ER) area of the caudal ventral respiratory group (cVRG) was investigated in anesthetized, vagotomized, paralyzed and artificially ventilated cats. ER neurons in both the ipsi- and the contralateral cVRG displayed excitatory responses to Bo¨t. c. electrical microstimulation. They were also activated by microinjections of d,l-homocysteic acid into the Bo¨t. c. region. We propose that at least part of the Bo¨t. c. projections to the cVRG have an excitatory function

Extensive monosynaptic inhibition of ventral respiratory group neurons by augmenting neurons in the Bötzinger complex in the cat

Axonal projections and synaptic connectivity of expiratory Bötzinger neurons with an augmenting firing pattern (Bot-Aug neurons) to neurons in the ipsilateral ventral respiratory group (VRG) were studied in anaesthetized cats. Antidromic mapping revealed extensive axonal arborizations of Bot-Aug neurons (24 of 45) to the rostral or caudal VRG, with some having arbors in both regions. Of 234 pairs of neurons studied with intracellular recording and spike-triggered averaging, monosynaptic inhibitory postsynaptic potentials (IPSPs) were evoked in 49/221 VRG neurons by 38/98 Bot-Aug neurons. The highest incidence of monosynaptic inhibition was found in inspiratory bulbospinal neurons (10 of 23 tested). Evidence was also found for monosynaptic inhibition, by a separate group of Bot-Aug neurons, of expiratory bulbospinal neurons (12/58), while excitatory postsynaptic potentials (EPSPs) were identified in another two of these neurons. In addition, monosynaptic IPSPs were recorded from 13 of 53 identified laryngeal motoneurons, and from 14 of 100 respiratory propriobulbar neurons. Presumptive disynaptic IPSPs were recorded from 11 of the 221 VRG neurons. We conclude that Bot-Aug neurons exert widespread inhibition on all major neuron categories in the ipsilateral VRG, and should be regarded as an important element in shaping the spatiotemporal output pattern of both respiratory motoneurons and premotor neurons.

Mechanisms of abdominal muscle activation during vomiting

The possible contribution of spinal reflexes to abdominal muscle activation during vomiting was assessed in decerebrate cats. The activity of these muscles is partly controlled by bulbospinal expiratory neurons in the caudal ventral respiratory group (VRG). In a previous study it was found that the abdominal muscles are still active during vomiting after midsagittal lesion of the axons of these neurons between C1 and the obex (A.D. Miller, L.K. Tan, and I. Suzuki. J. Neurophysiol. 57: 1854-1866, 1987). The present experiments indicate that this postlesion activity was due to spinal stretch reflexes because 1) such midsagittal lesions eliminate abdominal muscle nerve activity during fictive vomiting in paralyzed cats in which there are no abdominal stretch reflexes, 2) the abdominal muscles are activated during vomiting by spinal reflexes after upper thoracic cord transections, and 3) the normal 100-ms delay between diaphragmatic and abdominal activation during vomiting is reduced to approximately 20-25 ms after both types of lesions, which is consistent with postlesion abdominal reflex activation. Our results also suggest that, during normal vomiting, abdominal stretch and tension reflexes have only a minor role if any and abdominal muscle activation is probably mediated primarily or exclusively by expiratory neurons in the caudal ventral respiratory group. However, our finding that phrenic activity is reduced both during vomiting after thoracic transections and during fictive vomiting after paralysis is consistent with a contribution of reflex activity from abdominal and/or intercostal muscles to phrenic discharge during normal vomiting.

Activation and block of NMDA receptors by fast application of agonist and antagonists : Mark L. Mayer, Morris Benveniste and Doris K. Patneau, Unit of Neurophysiology & Biophysics, LDN, NICHD, NIH, Bethesda, MD USA

Most of the neurons of the caudal ventral respiratory group (cVRG) are bulbospinal expiratory neurons that receive their main excitatory drive from more rostral, but not yet defined regions. This study was devoted to investigate the functional role of ionotropic excitatory amino acid (EAA) receptors in the excitatory drive transmission to cVRG expiratory neurons during eupnoeic breathing and some respiratory reflexes including cough induced by mechanical stimulation of the tracheobronchial tree. The experiments were performed on spontaneously breathing rabbits under pentobarbitone anesthesia making use of microinjections (30–50 nl) of EAA receptor antagonists into the cVRG. Phrenic nerve and abdominal muscle activities were recorded. Bilateral microinjections of 50 mM kynurenic acid (KYN), a broad-spectrum EAA antagonist, and 10 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA antagonist, or 5 mM 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX), a more specific non-NMDA antagonist, completely suppressed spontaneous rhythmic abdominal activity and reflex expiratory responses either to tracheal occlusion at end-inspiration (Breuer–Hering inflation reflex) or to expiratory threshold loading (5 cm H2O); they also suppressed both the inspiratory and expiratory components of the cough reflex. Spontaneous rhythmic abdominal activity and the reflex respiratory responses were strongly reduced, but not completely abolished by microinjections of 10 mM d(−)-2-amino-5-phosphonopentanoic acid (D-AP5), an NMDA antagonist. The results provide evidence that the excitatory drive to cVRG bulbospinal expiratory neurons during eupnoeic breathing and the investigated respiratory reflexes is mediated by EAA receptors. They also support the view that neurons located in the cVRG are not merely elements of the expiratory output system.

Intercostal and abdominal muscle afferent influence on caudal medullary expiratory neurons that drive abdominal muscles

Our objective was to determine if caudal ventral respiratory group (VRG) expiratory (E) neurons that drive abdominal expiratory motoneurons in the lumbar cord respond to intercostal and lumbar nerve afferent stimulation. Results showed that 92% of medullary E-neurons that were antidromically activated from the upper lumbar cord reduced their activity in response to stimulation of external and internal intercostal and lumbar nerve afferents. We conclude that afferent information from intercostal and abdominal muscle tendon organs has an inhibitory effect on caudal VRG E-neurons that drive abdominal expiratory motoneurons.

Brainstem projections to cats' upper lumbar spinal cord: implications for abdominal muscle control

Unilateral L 1 L 2 gray matter HRP injections labeled neurons bilaterally in nucleus retroambiguus (expiratory neuron region of caudal ventral respiratory group) and ventromedial reticular formation. Minor labeling occurred in raphe, vestibular, and medial parabrachial nuclei, lateral reticular formation, and C 1 C 2. Midsagittal lesions between C 1 and obex prevented nucleus retroambiguus labeling (except 1 contralateral cell adjacent an incomplete lesion), indicating that these neurons decussate between C 1 and obex and have collaterals that recross the spinal cord.