Inspiratory Neurons Research Articles

Activity of brainstem respiratory neurones just before the expiration-inspiration transition in the rat.

Inspiratory activity of the hypoglossal nerve (XIIn) often precedes that of the phrenic nerve (PHRn). By manipulating artificial respiration, this preceding activity (pre-I XIIn activity) can be lengthened or isolated prematurely (decoupled XIIn activity) without developing into overt PHRn-associated inspiratory bursts. We hypothesized that these pre-I and decoupled XIIn activities, collectively termed 'XIIn-w/o-PHRn activity', reflect certain internal states of the respiratory centre at the period just prior to the transition from the expiratory phase to the inspiratory phase. In decerebrate, neuromuscularly blocked and artificially ventilated rats, the firing properties of medullary respiratory neurones were examined during the period of the XIIn-w/o-PHRn activity. The majority of the inspiratory neurones examined could be classified into two types: one was active (XIIn-type) and the other was inactive (PHRn-type) during the XIIn-w/o-PHRn period. On the other hand, augmenting expiratory (E-AUG) neurones of the Bötzinger complex (BOT) and the caudal ventral respiratory group (VRG) fired intensively during this period. Their firing stopped at the onset of the overt inspiratory bursts in the XIIn and PHRn, suggesting that BOT E-AUG neurones inhibit PHRn-type, but not XIIn-type, inspiratory neurones. We hypothesize that XIIn-type inspiratory activity facilitates the phase change from expiration to inspiration, through activation of certain inspiratory neurones that inhibit the firing of BOT E-AUG neurones and generation of the overt inspiratory bursts in XIIn-type and PHRn-type inspiratory neurones.

Opioid-Induced Quantal Slowing Reveals Dual Networks for Respiratory Rhythm Generation

Current consensus holds that a single medullary network generates respiratory rhythm in mammals. Pre-Bötzinger Complex inspiratory (I) neurons, isolated in transverse slices, and preinspiratory (pre-I) neurons, found only in more intact en bloc preparations and in vivo, are each proposed as necessary for rhythm generation. Opioids slow I, but not pre-I, neuronal burst periods. In slices, opioids gradually lengthened respiratory periods, whereas in more intact preparations, periods jumped nondeterministically to integer multiples of the control period (quantal slowing). These findings suggest that opioid-induced quantal slowing results from transmission failure of rhythmic drive from pre-I neurons to preBötC I networks, depressed below threshold for spontaneous rhythmic activity. Thus, both I (in the slice), and pre-I neurons are sufficient for respiratory rhythmogenesis.

Response of the respiratory network of mice to hyperthermia.

Most mammals modulate respiratory frequency (RF) to dissipate heat (i.e., panting) and avoid heat stroke during hyperthermic conditions. During hyperthermia, the RF of intact mammals increases and then declines or ceases (apnea). It has been proposed that this RF modulation depends on the presence of higher brain structures such as the hypothalamus. However, the direct effects of hyperthermia on the respiratory neural network have not been examined. To address this issue, the respiratory neural network [i.e., ventral respiratory group (VRG)] was isolated in a brain stem preparation taken from the medulla of mice (P0 -P6). Integrated population activity, predominated by inspiratory neurons, was recorded extracellularly from VRG neurons. The bath temperature was then heated from 30 to 40 degrees C, resulting in a biphasic frequency response in VRG activity. Following an initial six- to sevenfold increase and subsequent decline, fictive RF was maintained at a frequency that was higher than baseline frequency; at 40 degrees C, the RF was maintained at about two to four times that at 30 degrees C. The inspiratory burst amplitude and duration were significantly reduced during hyperthermic conditions. An increase in RF and decrease in VRG burst amplitude and duration also occurred when heating from 37 to 40 degrees C. Fictive apnea typically occurred during cooling to the control temperature. Furthermore, changes in hypoglossal motor nucleus activity paralleled those of the VRG, suggesting that temperature modulation of the VRG is likely to have a behaviorally relevant impact on respiration. We conclude that the VRG activity itself is modulated during hyperthermia and the respiratory network is particularly sensitive to temperature changes.

Activity of neurons in ventrolateral respiratory groups during swallowing in decerebrate rats

To elucidate the neuronal basis of the coordination between swallowing and respiration, we examined the swallowing-related activity of respiratory neurons in the ventrolateral respiratory groups of the medulla oblongata of decerebrate, paralyzed and artificially ventilated rats ( n=14). Extracellular recording was made during fictive swallowing evoked by the electrical stimulation of the superior laryngeal nerve from a total of 141 neurons with respiratory rhythm (99 expiratory and 42 inspiratory neurons). The burst of discharge by the hypoglossal nerve was used to monitor the pharyngeal phase of swallowing. The decrementing-expiratory (E-DEC) neurons ( n=62) were activated during ( n=46) or after ( n=10) the hypoglossal bursts, or showed no swallowing-related activity ( n=6). All of the augmenting-expiratory (E-AUG) neurons ( n=37) were silent during the hypoglossal bursts but were activated after each swallow. Inspiratory neurons showed either no swallowing-related bursts ( n=27), or were activated after the hypoglossal bursts ( n=15). Activation of the majority of E-DEC neurons may be related to the arrest of respiration during swallowing, and the post-swallow activation of E-AUG neurons may correspond to the expiratory phase that follows swallowing. We suggest that these behaviors of expiratory neurons are essential in the phase resetting of the respiratory cycle in association with the swallowing.

Salicylate action on medullary inspiratory neuron activity in a brainstem-spinal cord preparation from newborn rats.

Salicylate affects central respiratory control. The inspiratory neurons are the most important component of the medullary respiratory control center because they modulate the final motor output via the phrenic nerve. We investigated changes in burst rate, intraburst firing frequency, and membrane properties of inspiratory neurons in the isolated brainstem after the administration of salicylate. Newborn rat brainstem-spinal cord preparations were superfused with salicylate. Whole-cell recordings were performed from inspiratory neurons. Application of 1 mM salicylate caused an increase in the inspiratory neuronal burst rate from 6.9 +/- 1.6 bursts/min to 8.2 +/- 1.9 bursts/min (P < 0.05). The inspiratory neuron burst rate decreased from 8.3 +/- 0.7 bursts/min to 4.5 +/- 1.1 bursts/min after the application of 10 mM salicylate (P < 0.01). The depressant effect of 10 mM salicylate was antagonized by the gamma-aminobutyric acid (GABA) receptor antagonist bicuculline (1 microM). Resting membrane potential and intraburst firing frequency did not change with the application of salicylate and bicuculline even when the burst rate did change. We conclude that the effects of salicylate on the medullary inspiratory neurons are mainly due to a presynaptic action. GABAergic mechanisms are probably involved in the salicylate-induced central respiratory depression.

Differential Processing of Excitation by GABAergic Gain Modulation in Canine Caudal Ventral Respiratory Group Neurons

The discharge frequency (F(n)) patterns of medullary respiratory premotor neurons are subject to potent tonic GABAergic gain modulation. Studies in other neuron types suggest that the synaptic input for tonic inhibition is located on the soma where it can affect total neuronal output. However, our preliminary data suggested that excitatory responses elicited by highly local application of glutamate receptor agonists are not gain modulated. In addition, modulation of the amplitude of spike afterhyperpolarizations can gain modulate neuronal output, and this mechanism is located near the spike initiation zone and/or soma. The purpose of this study was to determine if these two gain-modulating mechanisms have different functional locations on the somatodendritic membrane of bulbospinal inspiratory and expiratory neurons. Four-barrel micropipettes were used for extracellular single-neuron recording and pressure ejection of drugs in decerebrate, paralyzed, ventilated dogs. The net increases in F(n) due to repeated short-duration picoejections of the glutamate receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), was quantified before and during locally induced antagonism of GABA(A) receptors by bicuculline or small-conductance, calcium-activated potassium channels by apamin. The AMPA-induced net increases in F(n) were not significantly altered by BIC, although it produced large increases in the respiratory-related activity. However, the AMPA-induced net responses were amplified in accordance with the gain increase of the respiratory-related activity by apamin. These findings suggest that GABAergic gain modulation may be functionally isolated from the soma/spike initiation zone, e.g., located on a dendritic shaft. This could allow other behavioral signals requiring strong neuronal activation (e.g., coughing, sneezing, vomiting) to utilize the same neuron without being attenuated by the GABAergic modulation.

Salicylate Action on Medullary Inspiratory Neuron Activity in a Brainstem-Spinal Cord Preparation from Newborn Rats

Salicylate Action on Medullary Inspiratory Neuron Activity in a Brainstem-Spinal Cord Preparation from Newborn Rats

Effects of controller dynamics on simulations of irregular and periodic breathing.

It is now clear that irregularities and instabilities in ventilation can result from the fact that there is feedback in the respiratory control system. This largely accounts for various forms of periodic breathing including Cheyne-Stokes respiration, central apneas during non-REM sleep, and the transient apneas that sometimes occur even in awake healthy people after periods of voluntary hyperventilation or with hypoxia.lt is even possible that obstructive sleep apneas in part occur by differences in the effects of feedback on chest wall compared to upper airway muscles. These disturbances in breathing can be reproduced by feedback models of chemical control and often can be caused experimentally by interventions and system changes suggested by the mathematical models. However there remain instances, as in the apneas that appear in REM sleep or in premature infants that are difficult to explain simply by feedback problems. In current models aiming at simulating periodic breathing, the respiratory controller as shown in Figure 2 is treated as a black box, which generates respiratory patterns as sine waves of airflow (Longobardo et al. 2002). The relationship between frequency and tidal volume is expressed by one or more linear equations. Although the complexities of respiratory generation have been appreciated for years, only relatively recently has the construction of mathematical models of the respiratory pattern generation been attempted. Moreover quite recently it has been recognized that the production of the respiratory pattern may involve pacemaker neurons as well as mutually inhibitory networks of inspiratory and expiratory neurons (Butera et al. 1999). But the effects of these newer concepts on breathing when included in feedback models of respiratory regulation have not been studied.

A combined blockade of glycine and calcium-dependent potassium channels abolishes the respiratory rhythm

In order to test whether glycinergic inhibition is essential for the in vivo respiratory rhythm, we analysed the discharge properties of neurones in the medullary respiratory network after blockade of glycine receptors in the in situ perfused brainstem preparation of mature wild type and oscillator mice with a deficient glycine receptor. In wild type mice, selective blockade of glycine receptors with low concentrations of strychnine (0.03–0.3 μM) provoked considerable changes in neuronal discharge characteristics: The cycle phase relationship of inspiratory, post-inspiratory and expiratory specific patterns of membrane potential changes was altered profoundly. Inspiratory, post-inspiratory and expiratory neurones developed a propensity for fast voltage oscillations that were accompanied by multiple burst discharges. These burst discharges were followed by “after-burst” hyperpolarisations that were capable of triggering secondary burst discharges. Blockade of glycine receptors and the “big” Ca 2+-dependent K +-conductance by charybdotoxin (3.3 nM) resulted in loss of the respiratory rhythm, whilst only tonic discharge activity remained. In contrast, rhythmic activity was only weakened, but preserved after the “small” Ca 2+-dependent activated K + conductance was blocked with apamin (8 nM). Also low concentrations of pentobarbital sodium (6 mg/kg) abolished rhythmic respiratory activity after blockade of glycine receptors in the wild type mice and in glycine receptor deficient oscillator mice. The data imply that failure of glycine receptors provokes enhanced bursting behaviour of respiratory neurones, whilst the additional blockade of BKCa channels by charybdotoxin or with pentobarbital abolishes the respiratory rhythm.

Histaminergic modulation of the intact respiratory network of adult mice.

Histaminergic modulation of neuronal activity in the respiratory network was investigated under normoxic and hypoxic conditions in the working heart-brainstem preparation of adult mice. Systemic application of histamine, as well as the H-1 and H-3 receptor agonists 6-[2-(4-imidazolyl)ethylamino]- N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT) and imetit, 0.5-10 micro M, significantly increased the frequency of respiratory burst discharges. Dimaprit, an H-2 receptor agonist, had no effect on respiratory activity. To test for ongoing histaminergic modulation we applied the histamine receptor antagonists pyrilamine (H-1); cimetidine (H-2) and thioperamide (H-3), each 0.5-10 micro M. Only the H-1 receptor antagonist had significant effects, viz. reduction of respiratory frequency and depression of burst amplitude. Underlying effects of histamine receptor activation were identified at the cellular level. Intracellular recordings showed that histamine mediated an increase in synaptic drive potentials in inspiratory neurones while augmentation of inhibitory and excitatory synaptic activity was observed in expiratory neurones. The augmented synaptic depolarisation of inspiratory neurones was blocked by the H-1 receptor antagonist. Histaminergic modulation is also involved in the hypoxic response of the respiratory network. Blockade of H-1 receptors significantly attenuated secondary depression of the biphasic hypoxic responses, while hypoxic augmentation was not affected. We conclude that histamine is a functional neuromodulator, which is tonically active in the respiratory network and is activated further during hypoxia. The data indicate that histaminergic neuromodulation acts predominantly via H-1 receptors.

Inspiratory augmenting bulbospinal neurons express both glutamatergic and enkephalinergic phenotypes.

Many of the inspiratory augmenting (I-AUG) neurons of the rostral ventral respiratory group (rVRG) are premotor neurons that excite phrenic motor neurons during inspiration, probably by releasing glutamate. In the present study, we demonstrate that these neurons are indeed glutamatergic, in that their cell bodies contain vesicular glutamate transporter-2 (VGLUT2) mRNA and spinal terminals from neurons in the region of the rVRG contain VGLUT2 protein. We also demonstrate by using parallel in situ hybridization and immunocytochemical evidence that most rVRG inspiratory premotor neurons are enkephalinergic. After iontophoretic deposits of biotinylated dextran amine (BDA) in the area of the rVRG, many BDA-labeled terminals in the ventral horn of cervical spinal cord (C4-C5) were immunoreactive for enkephalin and VGLUT2. Injections of Fluoro-Gold amidst phrenic motor neurons in C4-C5 labeled neurons in the area of the rVRG that contained both VGLUT2 mRNA and preproenkephalin (PPE) mRNA as revealed by double in situ hybridization. Thirty-eight bulbospinal I-AUG neurons were recorded in the rVRG and filled with biotinamide by using the juxtacellular labeling technique. Every biotinamide-filled cell tested was positively labeled for VGLUT2 mRNA (n = 14), and most of the cells tested in a separate population exhibited PPE mRNA (16/18). We conclude that most of the phrenic inspiratory premotor neurons of the rVRG are glutamatergic neurons that may also release enkephalins.

Persistent sodium current, membrane properties and bursting behavior of pre-bötzinger complex inspiratory neurons in vitro.

We measured persistent Na(+) current and membrane properties of bursting-pacemaker and nonbursting inspiratory neurons of the neonatal rat pre-Bötzinger complex (pre-BötC) in brain stem slice preparations with a rhythmically active respiratory network in vitro. In whole-cell recordings, slow voltage ramps (</=100 mV/s) inactivated the fast, spike-generating Na(+) current and yielded N-shaped current-voltage relationships with nonmonotonic, negative-slope regions between -60 and -35 mV when the voltage-sensitive component was isolated. The underlying current was a TTX-sensitive persistent Na(+) current (I(NaP)) since the inward current was present at slow voltage ramp speeds (3.3-100 mV/s) and the current was blocked by 1 microM TTX. We measured the biophysical properties of I(NaP) after subtracting the voltage-insensitive "leak" current (I(Leak)) in the presence of Cd(2+) and in some cases tetraethylammonium (TEA). Peak I(NaP) ranged from -50 to -200 pA at a membrane potential of -30 mV. Decreasing the speed of the voltage ramp caused time-dependent I(NaP) inactivation, but this current was present at ramp speeds as low as 3.3 mV/s. I(NaP) activated at -60 mV and obtained half-maximal activation near -40 mV. The subthreshold voltage dependence and slow inactivation kinetics of I(NaP), which closely resemble those of I(NaP) mathematically modeled as a burst-generation mechanism in pacemaker neurons of the pre-BötC, suggest that I(NaP) predominantly influences bursting dynamics of pre-BötC inspiratory pacemaker neurons in vitro. We also found that the ratio of persistent Na(+) conductance to leak conductance (g(NaP)/g(Leak)) can distinguish the phenotypic subpopulations of bursting pacemaker and nonbursting inspiratory neurons: pacemaker neurons showed g(NaP)/g(Leak) > g(NaP)/g(Leak) in nonpacemaker cells (P < 0.0002). We conclude that I(NaP) is ubiquitously expressed by pre-BötC inspiratory neurons and that bursting pacemaker behavior within the heterogeneous population of inspiratory neurons is achieved with specific ratios of these two conductances, g(NaP) and g(Leak).

Upper thoracic respiratory interneurons integrate noxious somatic and visceral information in rats.

The aim of this study was to determine if thoracic respiratory interneurons (TRINs) might receive peripheral noxious somatic and visceral inputs. Extracellular potentials of 78 respiration-related T(3) neurons, whose activity was driven by central respiratory output, were recorded from the intermediate zone in pentobarbital anesthetized, paralyzed, and ventilated male rats. These neurons were identified as interneurons by their locations and by the absence of antidromic activation from the cervical sympathetic trunk and cerebellum. Thoracic esophageal distension (ED) was produced by water inflation of a latex balloon (0.1-0.5 ml, 20 s). A catheter was placed in the pericardial sac to administer 0.2 ml bradykinin (10(-5) M) for noxious cardiac stimulation. Of 78 TRINs examined for ED, activity of 24 TRINs increased and activity of 8 TRINs decreased. Intrapericardial bradykinin increased activity in 26/65 TRINs tested and decreased activity in 5 TRINs. Seventy-four TRINs were tested for effects of brush, pressure, and pinch of the chest and upper back areas. No TRINs responded to brushing hair. Low-threshold responses to pressure were observed in 27 TRINs. Fourteen TRINs were wide dynamic range and 4 TRINs had high-threshold responses. Peripheral stimuli affected all types of TRINs, including inspiratory, expiratory, and biphasic neurons. Simultaneous phrenic recordings showed that effects of various somatic and visceral stimuli on TRINs were independent of central respiratory drive. Various somatovisceral and viscerovisceral patterns of input were observed in TRINs. The results suggested that TRINs participate in intraspinal processing and integration of nociceptive information from somatic fields and visceral organs.

Pharmacology of nicotinic receptors in preBötzinger complex that mediate modulation of respiratory pattern.

Nicotine regulates respiratory pattern by modulating excitatory neurotransmission affecting inspiratory neurons within the preBötzinger Complex (preBötC). The nicotinic acetylcholine receptor (nAChR) subtypes mediating these effects are unknown. Using a medullary slice preparation from neonatal rat, we recorded spontaneous respiratory-related rhythm from the hypoglossal nerve (XIIn) and patch-clamped inspiratory neurons in the preBötC simultaneously. The alpha7 nAChR antagonists alpha-bungarotoxin or methyllycaconitine (MLA) had little effect on the actions of low concentrations of nicotine (0.5 microM), which included an increase in respiratory frequency; a decrease in amplitude of XIIn inspiratory bursts; a tonic inward current associated with an increase in membrane noise; an increase in the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), and; a decrease in the amplitude of inspiratory drive current in voltage-clamped preBötC inspiratory neurons. These nicotinic actions were completely reversed by dihydro-beta-erythroidine (DH-beta-E) or hexamethonium and reduced by D-tubocurarine. Comparable concentrations of RJR-2403 (0.5-1 microM), an agonist selective for alpha4beta2 nAChRs, increased respiratory frequency to 186% and decreased the amplitude of XIIn inspiratory bursts to 83% of baseline. In voltage-clamped preBötC inspiratory (including pacemaker) neurons, RJR-2403 induced a tonic inward current of -15.2 pA associated with an increase in membrane noise, increased the frequency to 157% and amplitude to 106% of spontaneous EPSCs, and decreased the amplitude of inspiratory drive current to 80% of baseline. MLA had little effect on RJR-2403 actions, while DH-beta-E completely reversed them. These results suggest that the predominant subtype of nAChRs in preBötC in neonatal rats that mediates the modulation of respiratory pattern by low concentrations of nicotine is an alpha4beta2 combination and not an alpha7 subunit homomer. We do not exclude the possibility that co-assembly of alpha4beta2 with other subunits or other nAChR subtypes are also expressed in preBötC neurons. The parallel changes in the cellular and systems level responses induced by different nicotinic agonists and antagonists support the idea that modulation of excitatory neurotransmission affecting preBötC inspiratory neurons is a mechanism underlying the cholinergic regulation of respiratory pattern (). This study provides a useful model system for evaluating potential therapeutic cholinergic agents for their respiratory effects and side effects.

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.

Effects of GABA A and glycine receptor agonists on the medullary inspiratory neuronal activity during spontaneous augmented breaths in anesthetized rats

To clarify whether GABAergic or glycinergic transmission alters the activity of inspiratory neurons during spontaneous augmented breaths, we recorded the single unit activity from inspiratory neurons in the dorsal and ventral respiratory groups in the medulla of pentobarbital anesthetized rats and applied GABA A and glycine receptor agonists by iontophoresis using multibarrel microelectrodes. The spontaneous augmented breath was divided into two different phases; the first phase (phase I) resembled a normal inspiration but the second phase (phase II) indicated a marked increase in diaphragm electromyogram activity. During application of either muscimol or glycine, the discharge of inspiratory neurons during the phase I of spontaneous augmented breaths was suppressed, but the augmenting discharge of the phase II did not change significantly in any cell type of the neurons (I-augmenting, I-decrementing and I-other). These results suggested that the excitatory inputs to inspiratory neurons during the phase II of augmented breaths may not be significantly influenced by the activation of either GABA A receptors or glycine receptors.

Functional reconnections established by central respiratory neurons regenerating axons into a nerve graft bridging the respiratory centers to the cervical spinal cord.

The present work investigated, in adult rats, the long-term functional properties and terminal reconnections of central respiratory neurons regenerating axons within a peripheral nerve autograft bridging two separated central structures. A nerve graft was first inserted into the left medulla oblongata, in which the respiratory centers are located. Three months later, a C3 left hemisection was performed, and the distal tip of the graft was implanted into the C4 left spinal cord at the level of the phrenic nucleus, a natural central inspiratory target. Six to eight months after medullary implantation, the animals (n = 12) were electrophysiologically investigated to test 1) the phrenic target reinnervation by analyzing the phrenic responses elicited by bridge electrical stimulation and 2) the bridge innervation by unitary recordings of the spontaneous activity of regenerated axons within the nerve bridge. In the control group (n = 6), the medullary site of implantation corresponded to the dorsolateral medulla, a region known to be an unsuitable site for inducing respiratory axonal regrowth after nerve grafting. Stimulation of the nerve bridge never elicited phrenic nerve response, and no respiratory units were found within the nerve bridge. In the experimental group (n = 6), the proximal tip of the nerve bridge was implanted within the ventrolateral medulla at the level of the respiratory centers. Electrical stimulation of the nerve bridge induced phrenic nerve responses that reflected a postsynaptic activation of the phrenic target. Subsequent unitary recordings from teased fibers within the bridge revealed the presence of regenerated inspiratory fibers exhibiting discharge patterns typical of medullary inspiratory neurons, which normally make synaptic contacts with the inspiratory phrenic target. These results indicate that, when provided with an appropriate denervated target, central respiratory neurons with regenerated axons along a nerve bridge can remain functional for a long period and can make precise and specific functional reconnections with central homotypic target neurons.

Effects of Halothane (HAL) on Inhibitory Neurotransmission to Medullary Inspiratory (I) Neurons in a Decerebrate Dog Model

Effects of Halothane (HAL) on Inhibitory Neurotransmission to Medullary Inspiratory (I) Neurons in a Decerebrate Dog Model

Effects of Halothane (HAL) on Excitatory Neurotransmission to Medullary Inspiratory (I) Neurons in a Decerebrate Dog Model

Effects of Halothane (HAL) on Excitatory Neurotransmission to Medullary Inspiratory (I) Neurons in a Decerebrate Dog Model

Synaptic mechanisms of inspiratory off-switching evoked by pontine pneumotaxic stimulation in cats.

To elucidate synaptic mechanisms and the involvement of N-methyl-D-aspartate (NMDA) receptors in inspiratory off-switching (IOS) evoked by the stimulation of the nucleus parabrachialis medialis (NPBM), excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) were recorded from bulbar augmenting inspiratory (aug-I) and postinspiratory (PI) neurons in vagotomized cats. Stimulation of NPBM produced either transient inhibition or premature termination of inspiration (reversible or irreversible IOS), depending on the stimulus intensity. Each neuron displayed four-phasic postsynaptic responses during the reversible IOS, i.e. Phase 1 EPSPs, Phase 2 IPSPs, Phase 3 EPSPs and Phase 4 IPSPs in aug-I neurons, and Phase 1 plus 2 EPSPs, Phase 3 IPSPs and Phase 4 EPSPs in PI neurons. During the irreversible IOS, Phase 4 responses were replaced by sustained hyperpolarization in aug-I neurons and decrementing depolarization in PI neurons. Blockade of NMDA receptors by dizocilpine (0.3 mg kg(-1) i.v.) selectively increased Phase 4 potentials in both types of neurons and decreased the thresholds for evoking the irreversible IOS. The NPBM-induced responses had a pattern and time-course similar to those induced by vagal stimulation. The present results suggest that pneumotaxic and vagal inputs converge on the common IOS circuit, and the effectiveness of both inputs is modulated by NMDA receptors.