Medullary Mechanisms Research Articles

Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex.

Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia. Abnormalities in SP neurotransmission may therefore result in autonomic dysfunction during sleep and contribute to SIDS deaths. [125I] Bolton Hunter SP autoradiography was used to map the distribution and density of the SP, NK1R to 13 specific nuclei intimately related to cardiorespiratory function and autonomic control in the human infant medulla of 55 SIDS and 21 control (non-SIDS) infants. Compared to controls, SIDS cases exhibited a differential, abnormal developmental profile of the SP/NK1R system in the medulla. Furthermore the study revealed significantly decreased NK1R binding within key medullary nuclei in SIDS cases, principally in the nucleus tractus solitarii (NTS) and all three subdivisions of the inferior portion of the olivo-cerebellar complex; the principal inferior olivary complex (PIO), medial accessory olive (MAO) and dorsal accessory olive (DAO). Altered NK1R binding was significantly influenced by prematurity and male sex, which may explain the increased risk of SIDS in premature and male infants. Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and motor responses to life threatening challenges during sleep. These observations support the concept that abnormalities in a multi-neurotransmitter network within key nuclei of the medullary homeostatic system may underlie the pathogenesis of a subset of SIDS cases.

Age Associated Downregulation of Glutamate/GABA Transporters Expression in Rostral Ventral Lateral Medulla (RVLM)

Physiological function is altered with advancing age, including changes in sympathetic nervous system regulation. Studies focused on Glutamate/GABA ionotropic receptors using pharmacological agonists and antagonists in the rostral ventral lateral medulla (RVLM) indicates changes in medullary mechanisms regulating sympathetic nerve discharge (SND) in aged Fisher 344 rats. Identifying molecular mechanisms involved in this alteration is necessary to understand the regulation of central sympathetic neural circuits. Based on this rationale, we hypothesized that aging alters the basal regulation of RVLM Glutamate/GABA system‐associated genes. To test this hypothesis, the RVLM containing area was micro‐punched from young, middle‐aged and aged Fisher 344 rats. RNA level expression changes in RVLM GABA/Glutamate system‐associated genes were analyzed using RT2 profiler array and Taqman® real‐time PCR. Genes that showed >2fold differences in expression were analyzed at protein level by using immunoblot analysis. Downregulation of RVLM glutamate (Slc1a6) and GABA (Slc6a13) transporter genes was observed in aged compared with young rats at the RNA level, with a similar trend at the protein level. Slc1a6 and Slc6a13 transporters are known to modulate the amount of Glutamate/GABA in synaptic cleft and extra synaptic space. Down regulation of these transporters suggests there may be an altered Glutamergic/GABAergic balance in the aged RVLM.Support or Funding InformationSupported by NIH AG‐041948.

Gender features of sensorimotor function in young people with motor asymmetry

We have examined 745 healthy young adults aged 21,4±2,6 (including 493 men and 252-women) by using the appliance «Computer movements measurer». Having investigated the sexual features of sensor-motor function taking into account the motor asymmetry we have found that the most likely (p<0,05) differences between the central (switch of central units), subcortical (movement cycle durability) and medullary (reaction time to light) mechanisms of movements appear in left-handed women. The significant results show that there is the polynomial relationship between the left and right hand accuracy measures by taking into account the motor asymmetry in both men and women.

Analysis of RVLM Gene Expression in Young, Middle‐Aged and Aged F344 Rats

Abstract: The rostral ventral lateral medulla (RVLM) plays a critical role in regulation of basal sympathetic nerve discharge (SND). Advanced age is associated with altered regulation of SND, however, the effect of age on central medullary mechanisms regulating SND remains unknown. A series of experiments were initiated to identify cellular and molecular targets that may mediate age‐related changes in medullary regulation of SND. We tested the hypothesis that aging shifts the balance of RVLM excitatory and inhibitory influences towards excitation. Gene expression analysis was performed using Agilent Whole Rat Genome Microarray 4×44K followed by validation of microarray with TaqMan real‐time RT‐PCR and immunoblotting for specific RVLM proteins. Total RNA and protein were extracted from RVLM micropunches from young, middle‐aged and aged F344 rats. Microarray analysis revealed up‐regulation in aged compared to young and middle‐aged rats of several genes related to immune function and neurotransmitter receptors. Specifically, the chemokines CCL3, CCL4 and CCL5 were up‐regulated 3 to 4 fold in aged rats compared to young and middle‐aged rats. The results of previous studies suggest that increased chemokines in the brain can modulate NMDA receptor responses. The current preliminary results suggest that increased chemokine gene expression in the RVLM of aged rats may contribute to age‐related changes in SND regulation. Supported by NIH A6‐041948.

Facilitation of the respiratory rhythm in mice by acute exposure to a progestin, the etonogestrel. Involvement of medullary areas

Background Works have underlined the facilitatory influence of progestins on central respiratory drive (CRD). The congenital central hypoventilation syndrome (CCHS) is a neuro-respiratory disease characterized by an alteration of the CO 2 /H + chemosensitivity due to dysfunction of CO 2 /H + chemosensitive/PHOX2b-positive neurons of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). In our laboratory, a recovery of the CO 2 /H + chemosensitivity was fortuitously observed in two CCHS women who took a potent synthetic progestin, the desogestrel (Respir Physiol Neurobiol 2010;171:171–4). Objective Our aim was to appreciate the effects of an acute exposure to etonogestrel (ETO), the main active metabolite of the desogestrel, on the CRD and to determine its medullary action mechanisms. Methods We used: – an analysis of the effect of ETO (0.05–2 μM) on the CRD of ex vivo medullary-spinal cord preparations from newborn mice in both normopH and metabolic acidosis; – pharmacological co-application of ETO and muscimol or NMDA, agonists of GABA A or NMDA receptors known to be a target of some steroids; – an analysis of the c-fos expression in medullary respiratory structures. Results First, the respiratory frequency was: – dose-dependently increased in normopH by ETO (≈ +23–47%; P – increase by metabolic acidosis similarly under ETO (≈ +28–37% at 0.05–1 μM, P P P Second, changes in respiratory frequency induced by muscimol or NMDA at their EC 50 were more potent under ETO (≈ −60–63%, P P P P c-fos revealed ETO activated cells in respiratory medullary areas i.e. the ventrolateral medulla, nucleus of the solitary tract, RTN/pFRG and medullary raphe nuclei. Conclusions As a whole, data suggest that, by medullary mechanisms, the progestin ETO exerts a facilitatory influence on the CRD by acting at the level of respiratory structures. Involved mechanisms would implicate an interaction with GABA A and NMDA receptors. Besides, at least in newborn mice, ETO do not potentiate the respiratory response to metabolic acidosis by intrinsic medullary mechanisms.

Mylohyoid discharge of the in situ rat: a probe of pontile respiratory activities in eupnea and gasping

Our purpose was to characterize respiratory-modulated activity of the mylohyoid nerve. Since its motoneurons are in the trigeminal motor nucleus, mylohyoid discharge could serve as a probe of the role of pontile mechanisms in the generation of respiratory rhythms. Studies were performed in the decerebrate, perfused in situ preparation of the rat. Phrenic discharge was recorded as the index of the respiratory rhythm. In eupnea, the mylohyoid nerve discharged primarily during neural expiration, in the period between phrenic bursts. This expiratory discharge increased greatly in hypoxia and fell in hypercapnia. The hypoxia-induced increase in mylohyoid discharge was due, at least in part, to a direct influence of hypoxia on the brain stem. In ischemia, phrenic discharge increased, and then declined to apnea, which was succeeded by gasping. The mylohyoid nerve discharged tonically during the apneic period, but still declined during each of the phrenic bursts of gasping. This maintenance of a respiratory-modulation of the mylohyoid discharge in gasping supports the concept that a release of medullary mechanisms, rather than a ubiquitous suppression of pontile influences, underlies the neurogenesis of gasping. Results also provide additional support for our conclusion that activity of any single cranial nerve does not provide an accurate index of the type of respiratory rhythm, be it eupnea or gasping.

Commentaries on Viewpoint: Central chemoreception is a complex system function that involves multiple brain stem sites

to the editor: Amniote vertebrates adjust the acid-base status of the blood through ventilatory alterations of PaCO2 and, to some degree, by renal modulation of bicarbonate concentration. Receptor systems for the ventilatory acid-base regulation has been studied mainly in mammals, in which the

Pathogenetic role of myelitis for syringomyelia

Background CSF-flow obstruction is regarded as a mandatory factor for the development of syringomyelia. However, there are conditions in which syringomyelia is not associated with evident persistent CSF-flow obstruction, as in the case of inflammatory spinal cord lesions. In these instances we hypothesize that the accumulation of vasogenic edema may play a role in the development of the syrinx. Recently proposed theories underline, even in the event of CSF-flow obstructions, a major role for the accumulation and final coalescence of interstitial spinal fluid, rather than CSF penetration through the spinal cord. Aim To clarify the relationship between syrinx development and spinal cord inflammation, through the analysis of the role of intrinsic medullary factors versus CSF-flow block. Methods A prospective case series including patients with transient syringomyelia associated with different examples of non-infectious myelitis: sarcoidosis, post-infectious transverse myelitis, Devic's disease and multiple sclerosis. Cavitations resulting from cystic myelomalacia were excluded. CSF-flow block was assessed by structural MRI. Results Syringes associated with myelitis shared some common features: they developed during the acute phase of myelitis and disappeared after steroids, were all non-communicating cavitations involving the central canal, and occurred in the same spinal segment affected by myelitis. CSF-flow obstruction was detected in one patient (Chiari I malformation), while in the other three patients we could not detect anatomical predispositions. Conclusion Only one patient had structural abnormalities, though without evidence of a pathogenetic role in itself: however, CSF space obstruction and reduced CSF compliance could have accelerated the development of syringomyelia triggered by intramedullary inflammation. The clinical and radiological features in this patient are consistent with the label “presyringomyelia”. The absence of any anatomical predisposition in the other patients suggests a major pathophysiological role for intrinsic medullary mechanisms, including blood–spinal cord barrier breakdown, impairment of extracellular fluid drainage, and leakage of subarachnoidal CSF into the nervous tissue.

Persistence of eupnea and gasping following blockade of both serotonin type 1 and 2 receptors in the in situ juvenile rat preparation

In severe hypoxia or ischemia, normal eupneic breathing is replaced by gasping, which can serve as a powerful mechanism for "autoresuscitation." We have proposed that gasping is generated by medullary neurons having intrinsic pacemaker bursting properties dependent on a persistent sodium current. A number of neuromodulators, including serotonin, influence persistent sodium currents. Thus we hypothesized that endogenous serotonin is essential for gasping to be generated. To assess such a critical role for serotonin, a preparation of the perfused, juvenile in situ rat was used. Activities of the phrenic, hypoglossal, and vagal nerves were recorded. We added blockers of type 1 and/or type 2 classes of serotonergic receptors to the perfusate delivered to the preparation. Eupnea continued following additions of any of the blockers. Changes were limited to an increase in the frequency of phrenic bursts and a decline in peak heights of all neural activities. In ischemia, gasping was induced following any of the blockers. Few statistically significant changes in parameters of gasping were found. We thus did not find a differential suppression of gasping, compared with eupnea, following blockers of serotonin receptors. Such a differential suppression had been proposed based on findings using an in vitro preparation. We hypothesize that multiple neurotransmitters/neuromodulators influence medullary mechanisms underlying the neurogenesis of gasping. In greatly reduced in vitro preparations, the importance of any individual neuromodulator, such as serotonin, may be exaggerated compared with its role in more intact preparations.

Release of ATP in the ventral medulla during hypoxia in rats: role in hypoxic ventilatory response.

P2X2 receptor subunits of the ATP-gated ion channels are expressed by physiologically identified respiratory neurons in the ventral respiratory column, implicating ATP in the control of respiratory activity. We now show that, during hypoxia, release of ATP in the ventrolateral medulla (VLM) plays an important role in the hypoxic ventilatory response in rats. By measuring ATP release in real time at the ventral surface of the medulla with novel amperometric biosensors, we found that hypoxia (10% O2; 5 min) induced a marked increase in the concentration of ATP (approximately 3 microm). This ATP release occurred after the initiation of enhanced respiratory activity but coincided with the later hypoxia-induced slowing of the respiratory rhythm. ATP was also released at the ventral surface of the medulla during hypoxia in peripherally chemodenervated animals (vagi, aortic, and carotid sinus nerve sectioned). By using horizontal slices of the rat medulla, we found that, during hypoxia, ATP is produced throughout the VLM in the locations corresponding to the ventral respiratory column. Blockade of ATP receptors in the VLM (microinjection of P2 receptor antagonist pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid; 100 mum) augmented the hypoxia-induced secondary slowing of the respiratory rhythm. Our findings suggest that ATP released within the ventral respiratory column is involved in maintenance of the respiratory activity in conditions when hypoxia-induced slowing of respiration occurs. These data illustrate a new functional role for ATP-mediated purinergic signaling in the medullary mechanisms controlling respiratory activity.

Role of pontile mechanisms in the neurogenesis of eupnea

We have proposed a "switching concept" for the neurogenesis of ventilatory activity. Eupnea reflects the output of a pontomedullary neuronal circuit, whereas gasping is generated by medullary pacemaker mechanisms. Pontile mechanisms, then, are hypothesized to play a fundamental role in the neurogenesis of eupnea. If pontile mechanisms do play such a critical role, several criteria must be fulfilled. First, perturbations of pontile regions must alter eupnea under all experimental conditions. Second, neuronal activities that are consistent with generating the eupneic rhythm must be recorded in pons. Finally, medullary mechanisms alone cannot fully explain the neurogenesis of eupnea. Evidence from previous studies that support the validity of these criteria is presented herein. We conclude that pontile mechanisms play a critical role in the neurogenesis of eupnea.

Prolactin-releasing peptide affects pain, allodynia and autonomic reflexes through medullary mechanisms

Prolactin-releasing peptide (PrRP) and neuropeptide FF (NPFF) are RF-amide peptides expressed in brain areas involved in pain modulation. NPFF displays multiple effects on acute, inflammatory and neuropathic pain. The potential role of PrRP in pain was addressed by intrathecal and intracerebral injections of PrRP on pain-related responses in both neuropathic and normal rats. Particularly in the dorsal medulla, PrRP produced significant antinociception in normal rats and an antiallodynic effect in neuropathic rats. To understand the basis of PrRP-induced pain modulation, distributions of PrRP, PrRP receptor, and NPFF were compared in the rat central nervous system. PrRP and NPFF mRNA were expressed in different parts of the nucleus of the solitary tract. In the medulla, PrRP receptor mRNA expression was abundant only in area postrema. Of the peptides studied, only NPFF mRNA was found in the dorsal horn of the spinal cord and spinal nucleus of the trigeminal nerve. PrRP-immunoreactivity corresponded to the mRNA distribution. Even if the neuronal groups producing NPFF and PrRP were distinct, the fiber networks immunoreactive for PrRP and NPFF overlapped. The results show that PrRP modulates nociception due to supraspinal rather than spinal action, and that its antinociceptive mechanism differs from that previously characterized for NPFF.

Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X2 receptor subunit.

ATP is involved in central respiratory control and may mediate changes in the activity of medullary respiratory neurones during hypercapnia, thus playing an important role in central chemoreception. The main objective of this study was to explore further the role of ATP-mediated signalling in respiratory control and central chemoreception by characterising the profile of the P2X receptors expressed by physiologically identified respiratory neurones. In particular we determined whether respiratory neurones in the rostral ventrolateral medulla (VLM) express P2X2 receptor subunits of the ATP-gated ion channel, since ATP currents evoked at recombinant P2X2 receptors are potentiated by lowering extracellular pH. Experiments were performed on anaesthetised (pentobarbitone sodium 60 mg kg-1 I.P., then 10 mg kg-1 I.V. as required), gallamine-triethiodide-treated (10 mg kg-1 I.V., then 2-4 mg kg-1 h-1 I.V.) and artificially ventilated rats. The VLM respiratory neurones were classified according to the timing of their discharge pattern in relation to that of the phrenic nerve and by the exclusion of pump cells from the study population; these were labelled with Neurobiotin using the juxtacellular method, and visualised with fluorescence microscopy. It was found that a substantial proportion of the VLM respiratory neurones express the P2X2 receptor subunit. P2X2 receptor subunit immunoreactivity was detected in approximately 50 % (six out of 12) of expiratory neurones and in approximately 20 % (two out of 11) of neurones with inspiratory-related discharge (pre-inspiratory and inspiratory). In contrast, no Neurobiotin-labelled VLM respiratory neurones (n = 19) were detectably immunoreactive for the P2X1 receptor subunit. Microionophoretic application of ATP (0.2 M, 20-80 nA for 40 s) increased the activity of approximately 80 % (13 out of 16) of expiratory neurones and of approximately 30 % (five out of 18) of VLM neurones with inspiratory-related discharge. These effects were abolished by the P2 receptor blocker suramin (0.02 M, 80 nA), which also reduced the baseline firing in some expiratory neurones. These data indicate that modulation of P2X2 receptor function, such as that evoked by acidification of the extracellular environment during hypercapnia, may contribute to the changes in activity of the VLM respiratory neurones that express these receptors.

Effects of the neutral endopeptidase inhibitor thiorphan on cardiovascular and renal function in cirrhotic rats.

1. Cirrhosis is associated with cardiovascular and renal dysfunction including sodium retention. Many vasoactive peptides such as atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) are degraded by neutral endopeptidase 24.11 (NEP). We investigated the hemodynamic and renal effects of thiorphan, a NEP inhibitor, in a rat cirrhosis model. 2. Cirrhosis was induced by chronic bile duct ligation, and controls had sham operation. Systemic and renal hemodynamics in conscious, restrained animals were determined using radiolabeled microspheres, and glomerular filtration rate (GFR) was measured by (3)H-inulin clearance. Plasma ANP and ET-1, and renal cGMP and Na(+) - K(+) ATPase activity were assayed. These variables were measured at baseline and after intravenous infusion of thiorphan (0.5 mg kg(-1) loading dose followed by 0.1 mg kg(-1) min(-1) x 30 min). 3. Thiorphan significantly decreased cardiac output, and increased systemic vascular resistance in controls, whereas in cirrhotic rats these variables were unchanged. 4. Compared to the controls, cirrhotic rats showed a decreased baseline GFR and urine sodium excretion, and the latter was significantly increased by thiorphan. 5. Thiorphan increased plasma ET-1 levels in controls, but not cirrhotic rats. ANP levels were not significantly increased in either group by thiorphan. 6. Thiorphan significantly increased cGMP concentrations and decreased Na(+) - K(+) ATPase activity of renal medulla but not cortex in cirrhotic rats; no effect was observed in the control rats. 7. We conclude that thiorphan induces natriuresis in cirrhotic rats by a direct renal medullary mechanism via cGMP and Na(+) - K(+) ATPase, without affecting systemic hemodynamics. This may potentially be useful in patients with ascites.

Direct effect of Pa(CO2) on respiratory sinus arrhythmia in conscious humans.

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) and F(B). The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg (P < 0.05). Because V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.

Impact of NMDA Receptors and Nitric Oxide on pH Sensitivity of Medullary Mechanisms Controlling Respiratory Rhythm

We studied the dynamics of modifications of the respiratory activity generated by semi-isolated medullo-spinal preparations (SIMSP) of 3- to 4-day-old rats related to a drop in the pH of superfusing solution from 7.4 to 7.0. Reactions were recorded in the norm and under conditions of preliminary applications of a noncompetitive blocker of NMDA receptors, ketamine; an inhibitor of nitric oxide synthase (NOS), NG-nitro-L-arginine methyl ester (L-NAME); a substrate for NO synthesis, L-arginine; or an exogenous NO donor, sodium nitroprusside (SN). Under control conditions, test applications of the solution with pH 7.0 resulted in a significant increase in the frequency of inspiratory discharges (ID) recorded from the phrenic nerve and drops in their amplitude and integral intensity. Such SIMSP extracellular acidification-induced responses were inhibited in a dose-dependent manner by ketamine and L-NAME (the effect of the latter was more intensive). The effects of agents increasing the NO level in the tissues were not uniform: L-arginine potentiated an increase in the ID frequency related to application of the acidified solution, while SN inhibited such a reaction. Our findings allow us to suppose that the stimulating influences of the pH-sensitive chemoreceptor structures of the ventrolateral medulla (VLM) on the activity of the medullary respiratory generator of early postnatal rats are realized with the involvement of NMDA receptors of excitatory amino acids and the process of enzyme-mediated NO production. It seems probable that endogenous synthesis of NO in VLM structures mediates and potentiates the effect of activation of the NMDA receptors on the medullary generator of the respiratory rhythm.

Rostral medullary respiratory neuronal activities of decerebrate cats in eupnea, apneusis and gasping

Eupnea is generated by mechanisms within the pons and medulla. Following removal of pons or exposure to anoxia, gasping is elicited. Eupnea and gasping are markedly different ventilatory patterns. The genesis of gasping is dependent upon rostral medullary neuronal activities. To generate the gasp, these activities should commence before the phrenic burst. In decerebrate, vagotomized, paralyzed and ventilated cats, eupnea was altered to gasping in anoxia. Rostral medullary neuronal activities had inspiratory, expiratory and phase-spanning patterns in eupnea. During gasping, some inspiratory neuronal activities commenced before the phrenic gasp; these same neurons had commenced activities after the onset of the eupneic phrenic burst. Expiratory and phase-spanning neurons did not discharge. Neuronal activities which are consonant with a role in the neurogenesis of gasping had very different discharge patterns in eupnea. Results support the concept that medullary mechanisms for gasping are incorporated in the ponto–medullary circuit responsible for the neurogenesis and expression of eupnea.

Parameters of discharges of respiratory neurons of the ventrolateral medullary regions in early postnatal rats

In experiments on superfusedin situ semi-isolated medullo-spinal preparations (SIMSP) of newborn (1st day of life) and 4- to 5-day-old rats, we studied the parameters of extracellularly recorded spike activity of respiratory neurons of the ventrolateral medullary regions (VLMR). In SIMSP of 4- to 5-day-old rats, the frequency of discharges of pre-inspiratory, inspiratory, and expiratory neurons is shown to be significantly higher, while the dispersion of its values is considerably lower, as compared with the corresponding values for newborn animals. In the majority of pre-inspiratory and inspiratory neurons of SIMSP of newborn rats, irregular low-frequency discharges are usually generated within the interinspiration phase. The relative intensity of suppression of discharges of pre-inspiratory and expiratory neurons within an inspiration phase is much lower in SIMSP of newborn rats, as compared with that in 4- to 5-day-old preparations. The activity of most pre-inspiratory neurons manifests a trend toward transformation from a two-phase pattern in newborn rats (with two frequency peaks, pre- and post-inspiratory) to a monophasic pattern (with one pre-inspiratory frequency peak) typical of 4- to 5-day-old animals. The effects of electrical stimulation of the site of localization of pre-inspiratory neurons showed that in SIMSP of both age groups of rats an inspiratory response could be evoked in then. phrenicus only in the case when stimulation was applied within the second half of an interinspiratory phase. Therefore, it can be supposed that the respiratory network in newborn animals is to a considerable extent immature in the morphofunctional aspect. It seems probable that in early postnatal rats pre-inspiratory neurons are involved in the medullary mechanisms foron-off switching of the inspiratory and expiratory phases.

Expiratory neural activities in gasping induced by pharyngeal stimulation and hypoxia

The purpose was to characterize expiratory neural activities in gasping elicited during the aspiration reflex (AR) in hyperoxia and during hypoxia-induced gasping. In decerebrate, vagotomized and paralyzed cats, we recorded activities of inspiratory and expiratory cranial and spinal nerves. The AR was elicited by touching the epipharyngeal mucosa. In eupnea, spinal expiratory activities were greatly decreased during AR whereas laryngeal expiratory activities were increased. In hypoxia-induced gasping, both the laryngeal and spinal expiratory activities were reduced. All of the inspiratory activities were increased during both gasping and the AR. In addition, neural activities were below control levels following AR; activities gradually recovered to control levels. We conclude that spinal expiratory activities are inhibited during the AR and gasping. Results are consistent with the concept that medullary mechanisms for gasping are recruited by mechanical stimulation of the epipharynx. In hypoxia-induced gasping, the hypoxia, per se, causes a separate suppression of laryngeal expiratory activities.

Renalmedullary mechanisms in hypertension

Renalmedullary mechanisms in hypertension