Pre-Botzinger complex in the cat

1995 ◽  
Vol 73 (4) ◽  
pp. 1452-1461 ◽  
Author(s):  
S. W. Schwarzacher ◽  
J. C. Smith ◽  
D. W. Richter
Keyword(s):  
Spinal Cord ◽  
Neuronal Activity ◽  
Membrane Depolarization ◽  
Neonatal Rat ◽  
Respiratory Neurons ◽  
Spike Discharge ◽  
Inspiratory Phase ◽  
Inspiratory Neurons ◽  
Bötzinger Complex ◽  
Expiratory Neurons

1. Patterns of respiratory neuronal activity were examined in pentobarbitone anesthetized adult cats in a circumscribed area of the ventrolateral medulla, which has previously been defined as the pre-Botzinger complex (pre-BOTC) from electrophysiological and morphological criteria in the brain stem-spinal cord preparation of the neonatal rat. The pre-BOTC has been proposed to play a critical role in respiratory rhythm generation in mammals, but electrophysiological properties of the region have not been thoroughly characterized in the adult brain stem in vivo. 2. From intra- and extracellular recordings, we verified the existence of a well-defined zone with a distinct profile of neuronal activity between the rostral Botzinger complex containing expiratory neurons and the more caudal medullary pool of inspiratory neurons of the ventral respiratory group (VRG) in the para-ambigual region. This zone corresponds to the pre-BOTC. It was characterized by a concentration of the various types of respiratory neurons, particularly those proposed to be involved in respiratory phase transitions, including neurons discharging immediately before the onset of inspiratory phase activity (pre-inspiratory neurons), early-inspiratory, and postinspiratory neurons. The majority of these neurons were presumed interneurons because they were not antidromically activated by spinal cord or cranial nerve stimulation. 3. The locus of the pre-BOTC corresponded histologically to the rostral part of the nucleus ambiguus and ventrolateral reticular formation. It was located caudal to the retrofacial nucleus and rostral to the lateral reticular nucleus, extending 3.0-3.5 mm rostral to the obex, and 3.2-4.0 mm lateral from the midline. This location was homologous to that established in the neonatal rat. 4. Pre-inspiratory neurons (pre-I neurons) were specifically found in the pre-BOTC. Intracellular recordings from these neurons revealed two types of activity patterns. Type 1 of pre-I neurons exhibited a steady membrane depolarization during expiration and a steep membrane depolarization with a high-frequency burst of action-potential discharge during the phase transition from expiration to inspiration. This was followed by a decline of depolarization and spike discharge during the remainder of the inspiratory phase. A second type of pre-I neurons exhibited a secondary graded membrane depolarization and burst discharge during the late-inspiratory period. 5. Synaptic events were examined in other respiratory neurons during the 40-160 ms preceding the onset of phrenic nerve activity when pre-I neurons exhibited peak spike discharge. Early-inspiratory, throughout-respiratory, and postinspiratory neurons were disinhibited during this period, whereas stage-2 expiratory neurons exhibited a decrease in spike activity and repolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

2006 ◽  
Vol 290 (5) ◽  
pp. R1387-R1396 ◽  
Author(s):  
Peter M. Lalley
Keyword(s):  
Action Potential ◽  
Respiratory Rhythm ◽  
Input Resistance ◽  
Membrane Depolarization ◽  
Respiratory Neurons ◽  
Response Analysis ◽  
Inspiratory Neurons ◽  
Potential Shape ◽  
Expiratory Neurons

Opiates have effects on respiratory neurons that depress tidal volume and air exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive opioid effect is slowing of the respiratory rhythm through mechanisms that have not been thoroughly investigated. An in vivo dose-response analysis was performed on medullary respiratory neurons of adult cats to investigate two untested hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates suppress intrinsic conductances that limit discharge duration in medullary inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen the duration of discharges postsynaptically in phase-regulating postinspiratory and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate cats, a threshold dose (3 μg/kg) of the μ-opioid receptor agonist fentanyl slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory bulbospinal neurons. Additional doses (2–4 μg/kg) of fentanyl also lengthened the interburst silent periods in each type of neuron and delayed the rate of membrane depolarization to firing threshold without altering synaptic drive potential amplitude, input resistance, peak action potential frequency, action potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of inspiratory and expiratory neurons without altering peak membrane depolarization and hyperpolarization, input resistance, or action potential properties. The temporal changes evoked in the tested neurons can explain the slowing of network respiratory rhythm, but the lack of significant, direct opioid-mediated membrane effects suggests that actions emanating from other types of upstream bulbar respiratory neurons account for rhythm slowing.

scholarly journals Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats

2008 ◽  
Vol 109 (2) ◽  
pp. 233-242 ◽  
Author(s):  
Junya Kuribayashi ◽  
Shigeki Sakuraba ◽  
Masanori Kashiwagi ◽  
Eiki Hatori ◽  
Miki Tsujita ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Respiratory Depression ◽  
Motor Neurons ◽  
Type A ◽  
Aminobutyric Acid ◽  
Respiratory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Inspiratory Neurons ◽  
Acid Type ◽  
Bötzinger Complex

Background Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of gamma-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression. Methods In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the gamma-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques. Results Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons. Conclusion Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.

Differing activities of medullary respiratory neurons in eupnea and gasping

1991 ◽  
Vol 70 (3) ◽  
pp. 1265-1270 ◽  
Author(s):  
D. Zhou ◽  
M. J. Wasicko ◽  
J. M. Hu ◽  
W. M. St John
Keyword(s):  
Carbon Monoxide ◽  
Brain Stem ◽  
Phrenic Nerve ◽  
Peak Discharge ◽  
Discharge Frequency ◽  
Respiratory Neurons ◽  
Ventilatory Pattern ◽  
Medullary Respiratory Neurons ◽  
Inspiratory Neurons ◽  
Expiratory Neurons

Our purpose was to compare further eupneic ventilatory activity with that of gasping. Decerebrate, paralyzed, and ventilated cats were used; the vagi were sectioned within the thorax caudal to the laryngeal branches. Activities of the phrenic nerve and medullary respiratory neurons were recorded. Antidromic invasion was used to define bulbospinal, laryngeal, or not antidromically activated units. The ventilatory pattern was reversibly altered to gasping by exposure to 1% carbon monoxide in air. In eupnea, activities of inspiratory neurons commenced at various times during inspiration, and for most the discharge frequency gradually increased. In gasping, the peak discharge frequency of inspiratory neurons was unaltered. However, all commenced activities at the start of the phrenic burst and reached peak discharge almost immediately. The discharge frequencies of all groups of expiratory neurons fell in gasping, with many neurons ceasing activity entirely. These data are consistent with the hypothesis that brain stem mechanisms controlling eupnea and gasping differ fundamentally.

Persistent Sodium Current, Membrane Properties and Bursting Behavior of Pre-Bötzinger Complex Inspiratory Neurons In Vitro

2002 ◽  
Vol 88 (5) ◽  
pp. 2242-2250 ◽  
Author(s):  
Christopher A. Del Negro ◽  
Naohiro Koshiya ◽  
Robert J. Butera ◽  
Jeffrey C. Smith
Keyword(s):  
Sodium Current ◽  
Neonatal Rat ◽  
Membrane Properties ◽  
Negative Slope ◽  
Inactivation Kinetics ◽  
Pacemaker Neurons ◽  
Inspiratory Neurons ◽  
Voltage Ramp ◽  
Bötzinger Complex

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 μM TTX. We measured the biophysical properties of I NaP after subtracting the voltage-insensitive “leak” current ( I Leak) in the presence of Cd2+ 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 NaPinactivation, 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 Leakin 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.

The Effects of Nasal Flow Stimulation on Central Respiratory Pattern

1995 ◽  
Vol 9 (4) ◽  
pp. 203-208 ◽  
Author(s):  
Satoshi Nonaka ◽  
Akihiro Katada ◽  
Kizuku Nakajima ◽  
Takashi Ohsaki ◽  
Tokuji Unno
Keyword(s):  
Cycle Time ◽  
Suppressive Effect ◽  
Respiratory Cycle ◽  
Respiratory Pattern ◽  
Respiratory Neurons ◽  
Electromyographic Activity ◽  
Inspiratory Neurons ◽  
Expiratory Neurons ◽  
Flow Stimulation ◽  
Nasal Flow

The purpose of this study was to analyze the functional role of nasal afferents on central respiratory mechanisms. The electromyographic activity of the diaphragm and the neuronal activities of respiratory neurons within the brainstem were recorded during nasal flow stimulation, using decerebrate cats. Flow stimulation delivered to the nose prolonged the respiratory cycle time and decreased the amplitude of diaphragmatic activity. The respiratory cycle time was prolonged due to prolongation of expiratory phase. Cool air flow stimulation was more effective for changing the respiratory pattern than was warm air. All recorded inspiratory neurons of the dorsal respiratory group decreased their firing rate during stimulation, but more than half of expiratory neurons of the ventral respiratory group did not change. These results suggest that nasal afferents which respond to temperature can modulate the central respiratory pattern and have a stronger suppressive effect on the activity of inspiratory neurons than that of expiratory neurons.

Neural mechanisms of sneeze

1975 ◽  
Vol 229 (3) ◽  
pp. 770-776 ◽  
Author(s):  
HL Batsel ◽  
AJ Lines
Keyword(s):  
High Frequency ◽  
Neural Mechanisms ◽  
Nucleus Ambiguus ◽  
Respiratory Neurons ◽  
Similar Response ◽  
Response Patterns ◽  
Nerve Activity ◽  
Inspiratory Neurons ◽  
Expiratory Neurons ◽  
Stimulation Of

Sneezes were induced in anestized cats by repetitive stimulation of the ethmoidal nerve. Activity of bulbar respiratory neurons during sneezing was recorded extracellularly through tungsten microelectrodes. Most expiratory neurons could be locked onto the stimulus pulses so that they responded either throughout inspiration as well as expiration or so that they began responding at some time during inspiration. As inspiration approached termination, multiple spiking occurred, finally to result in high-frequency bursts which just preceded active expiration. A fraction of expiratory neurons were activated only in bursts. Latent expiratory neurons were recruited in sneezing. Inspiratory neurons near nucleus ambiguus and most of those near fasciculus solitarius displayed similar response patterns consisting of silent periods followed by delayed smooth activations. Temporal characteristics of the silent periods, "inhibitory gaps," suggested that they resulted from inhibition whose source was the expiratory neurons which were driven throughout inspriation. Some inspiratory neurons in the area of fasciculus solitarius failed to exhibit inhibitory gaps.

A study of sympathetic preganglionic neuronal activity in a neonatal rat brainstem-spinal cord preparation

1995 ◽  
Vol 52 (1) ◽  
pp. 51-63 ◽  
Author(s):  
Susan A. Deuchars ◽  
K.Michael Spyer ◽  
Penelope A. Brooks ◽  
Michael P. Gilbey
Keyword(s):  
Spinal Cord ◽  
Neuronal Activity ◽  
Neonatal Rat ◽  
Rat Brainstem

Quantal synaptic transmission in phrenic motor nucleus

1992 ◽  
Vol 68 (4) ◽  
pp. 1468-1471 ◽  
Author(s):  
G. Liu ◽  
J. L. Feldman
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Amplitude Distribution ◽  
Excitatory Synaptic Transmission ◽  
Neonatal Rat ◽  
Respiratory Neurons ◽  
Motor Nucleus ◽  
Patch Clamp Recording ◽  
Epsc Amplitude ◽  
Quantal Size

1. The quantal nature of excitatory synaptic transmission was studied in respiratory interneurons and phrenic motoneurons of intact neonatal rat brain stem-spinal cord preparations in vitro. Synaptic currents were recorded with whole-cell patch-clamp recording techniques. 2. Because the most important factor for quantal detection is the ratio of quantal size to quantal standard deviation, factors that influence this ratio were evaluated so that experimental techniques that enhance this ratio could be defined. 3. Under favorable conditions, we directly observed quantal amplitude fluctuations in spontaneous excitatory postsynaptic currents (EPSCs) in spinal cord respiratory neurons. The quantal conductance size was 55-100 pS. With fast decay of these EPSCs, the charge reaching the soma for a single quantum is only approximately 15 fC (Vh = -80 mV). 4. We also studied miniature EPSC amplitude distributions. These were skewed, as previously reported; however, distinct quantal intervals were observed. Furthermore, in three cells tested, the quantal size in the miniature EPSC amplitude distribution was similar to the quantal size in the spontaneous EPSC amplitude distribution. 5. We conclude that excitatory synaptic transmission in the mammalian spinal cord is quantal and that the apparent skewness of miniature EPSC distributions results from summation of events with multiple quantal peak amplitudes.

Thyrotropin-releasing hormone stimulates perinatal rat respiration in vitro

1996 ◽  
Vol 271 (5) ◽  
pp. R1160-R1164 ◽  
Author(s):  
J. J. Greer ◽  
Z. al-Zubaidy ◽  
J. E. Carter
Keyword(s):  
Spinal Cord ◽  
Brain Stem ◽  
Thyrotropin Releasing Hormone ◽  
Neonatal Rat ◽  
Discharge Frequency ◽  
Releasing Hormone ◽  
Respiratory Rhythmogenesis ◽  
Fetal Rat ◽  
Bötzinger Complex

In the present study, we test whether thyrotropin-releasing hormone (TRH) stimulates respiratory frequency in perinatal rats by acting at regions of the medulla responsible for respiratory rhythmogenesis, the pre-Botzinger complex. We also test whether TRH stimulates respiration in the fetal rat at a time shortly after the inception of respiratory rhythmogenesis [embryonic days (E) 17-18]. Two in vitro experimental models were utilized: the isolated brain stem-spinal cord preparation from fetal (E17-E18) and neonatal [postnatal days (P) 0-2] rats and the medullary slice preparation isolated from neonatal rats (P1-P2). Bath application of TRH caused a dose-dependent, reversible increase (maximum increase approximately 60%) in the frequency of respiratory rhythmic neural discharge generated by brain stem-spinal cord [half-maximal effective concentration (EC50) approximately 9 nM] and medullary slice (EC50 approximately 2.5 nM) neonatal rat preparations. Pressure injection of TRH unilaterally into the region of the pre-Botzinger complex of the neonatal medullary slice caused an approximately 28% increase in the frequency of respiratory discharge. Application of TRH to the medium bathing fetal rat brain stem-spinal cord preparations caused an approximately threefold increase in respiratory discharge frequency. We conclude that TRH stimulates respiratory discharge frequency from the time near inception of respiratory motor discharge and acts directly at the pre-Botzinger complex.

Respiratory neuronal activity during apnea and poststimulatory effects of laryngeal origin in the cat

2000 ◽  
Vol 89 (3) ◽  
pp. 917-925 ◽  
Author(s):  
Fulvia Bongianni ◽  
Donatella Mutolo ◽  
Marco Carfì ◽  
Giovanni A. Fontana ◽  
Tito Pantaleo
Keyword(s):  
Respiratory Depression ◽  
Superior Laryngeal Nerve ◽  
Respiratory Neurons ◽  
Inhibitory Input ◽  
Phase Theory ◽  
Inspiratory Neurons ◽  
Three Phase ◽  
Expiratory Neurons ◽  
Inspiratory Activity ◽  
Respiratory Reflexes

We investigated the behavior of medullary respiratory neurons in cats under pentobarbitone anesthesia, vagotomized, paralysed, and artificially ventilated to elucidate neural mechanisms underlying apnea and poststimulatory respiratory depression induced by superior laryngeal nerve (SLN) stimulation. Inspiratory neurons were completely inhibited during SLN stimulation and poststimulatory apnea. During recovery of inspiratory activity, augmenting inspiratory neurons were depressed, decrementing inspiratory neurons were excited, and late inspiratory neurons displayed unchanged bursts closely locked to the end of the inspiratory phase. Augmenting expiratory neurons were either silenced or displayed different levels of tonic activity during SLN stimulation; some of them were clearly activated. These expiratory neurons displayed activity during poststimulatory apnea, before the onset of the first recovery phrenic burst. Postinspiratory or decrementing expiratory neurons were activated during SLN stimulation; their discharge continued with a decreasing trend during poststimulatory apnea. The results support the three-phase theory of rhythm generation and the view that SLN stimulation provokes a postinspiratory apnea that could represent the inhibitory component of respiratory reflexes of laryngeal origin, such as swallowing. In addition, because a subpopulation of augmenting expiratory neurons displays activation during SLN stimulation, the hypothesis can be advanced that not only postinspiratory, or decrementing expiratory neurons, but also augmenting expiratory neurons may be involved in the genesis of apnea and poststimulatory phenomena. Finally, the increase in the activity of decrementing inspiratory neurons after the end of SLN stimulation may contribute to the generation of poststimulatory respiratory depression by providing an inhibitory input to bulbospinal augmenting inspiratory neurons.

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