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

1990 ◽  
Vol 81 (3) ◽  
pp. 639-648 ◽  
Author(s):  
C. Jiang ◽  
J. Lipski
Keyword(s):  
Ventral Respiratory Group ◽  
Bötzinger Complex ◽  
Monosynaptic Inhibition

Respiratory changes induced by kainic acid lesions in rostral ventral respiratory group of rabbits

2002 ◽  
Vol 283 (1) ◽  
pp. R227-R242 ◽  
Author(s):  
Donatella Mutolo ◽  
Fulvia Bongianni ◽  
Marco Carfì ◽  
Tito Pantaleo
Keyword(s):  
Kainic Acid ◽  
High Frequency ◽  
Rhythmic Activity ◽  
Respiratory Frequency ◽  
Ventral Respiratory Group ◽  
High Frequency Oscillations ◽  
Bötzinger Complex ◽  
Inspiratory Activity ◽  
Low Amplitude

The role played by the Bötzinger complex (BötC), the pre-Bötzinger complex (pre-BötC), and the more rostral extent of the inspiratory portion of the ventral respiratory group (iVRG) in the genesis of the eupneic pattern of breathing was investigated in anesthetized, vagotomized, paralyzed, and artificially ventilated rabbits by means of kainic acid (KA, 4.7 mM) microinjections (20–30 nl). Unilateral KA microinjections into all of the investigated VRG subregions caused increases in respiratory frequency associated with moderate decreases in peak phrenic amplitude in the BötC and pre-BötC regions. Bilateral KA microinjections into either the BötC or pre-BötC transiently eliminated respiratory rhythmicity and caused the appearance of tonic phrenic activity (“tonic apnea”), whereas injections into the rostral iVRG completely suppressed inspiratory activity. Rhythmic activity resumed as low-amplitude, high-frequency oscillations and displayed a progressive, although incomplete, recovery. Combined bilateral KA microinjections (BötC and pre-BötC) caused persistent (>3 h) tonic apnea. Results show that all of the investigated VRG subregions exert a potent control on both the intensity and frequency of inspiratory activity, thus suggesting that these areas play a major role in the genesis of the eupneic pattern of breathing.

scholarly journals Release of ATP by pre-Bötzinger complex astrocytes contributes to the hypoxic ventilatory response via a Ca2+ -dependent P2Y1 receptor mechanism

2017 ◽  
Vol 596 (15) ◽  
pp. 3245-3269 ◽  
Author(s):  
Vishaal Rajani ◽  
Yong Zhang ◽  
Venkatesh Jalubula ◽  
Vladimir Rancic ◽  
Shahriar SheikhBahaei ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
P2y1 Receptor ◽  
Hypoxic Ventilatory Response ◽  
Bötzinger Complex

Sodium Currents in Neurons From the Rostroventrolateral Medulla of the Rat

2003 ◽  
Vol 90 (3) ◽  
pp. 1635-1642 ◽  
Author(s):  
Ilya A. Rybak ◽  
Krzysztof Ptak ◽  
Natalia A. Shevtsova ◽  
Donald R. McCrimmon
Keyword(s):  
Sodium Channels ◽  
Sodium Current ◽  
Cell Voltage ◽  
Kinetic Properties ◽  
Persistent Sodium Current ◽  
Sodium Currents ◽  
Bötzinger Complex ◽  
Window Current ◽  
Bursting Activity

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15). Neurons were investigated using the whole cell voltage-clamp technique. Standard activation and inactivation protocols were used to characterize the steady-state and kinetic properties of the rapidly inactivating sodium current. Slow depolarizing ramp protocols were used to characterize the noninactivating sodium current. The “window” component of the rapidly inactivating sodium current was calculated using mathematical modeling. The persistent sodium current was revealed by subtraction of the window current from the total noninactivating sodium current. Our results provide evidence of the presence of persistent sodium currents in neurons of the rat rostroventrolateral medulla and determine voltage-gated characteristics of activation and inactivation of rapidly inactivating and persistent sodium channels in these neurons.

Botzinger complex region role in phrenic-to-phrenic inhibitory reflex of cat

1989 ◽  
Vol 67 (4) ◽  
pp. 1364-1370 ◽  
Author(s):  
D. F. Speck
Keyword(s):  
Nerve Stimulation ◽  
Phrenic Nerve ◽  
Inhibitory Response ◽  
Phrenic Nerve Stimulation ◽  
Bötzinger Complex ◽  
Before And After ◽  
Pass Through ◽  
Bilateral Lesions ◽  
Decerebrate Cats ◽  
Inhibitory Reflex

Neuronal recordings, microstimulation, and electrolytic and chemical lesions were used to examine the involvement of the Botzinger Complex (BotC) in the bilateral phrenic-to-phrenic inhibitory reflex. Experiments were conducted in decerebrate cats that were paralyzed, ventilated, thoracotomized, and vagotomized. Microelectrode recordings within the BotC region revealed that some neurons were activated by phrenic nerve stimulation (15 of 69 expiratory units, 9 of 67 inspiratory units, and 19 nonrespiratory-modulated units) at average latencies similar to the onset latency of the phrenic-to-phrenic inhibition. In addition, microstimulation within the BotC caused a short latency transient inhibition of phrenic motor activity. In 17 cats phrenic neurogram responses to threshold and supramaximal (15 mA) stimulation of phrenic nerve afferents were recorded before and after electrolytic BotC lesions. In 15 animals the inhibitory reflex was attenuated by bilateral lesions. Because lesion of either BotC neurons or axons of passage could account for this attenuation, in eight experiments the phrenic-to-phrenic inhibitory responses were recorded before and after bilateral injections of 5 microM kainic acid (30–150 nl) into the BotC. After chemical lesions, the inhibitory response to phrenic nerve stimulation remained; however, neuronal activity typical of the BotC could not be located. These results suggest that axons important in producing the phrenic-to-phrenic reflex pass through the region of the BotC, but that BotC neurons themselves are not necessary for this reflex.

scholarly journals Voltage-Dependent Rhythmogenic Property of Respiratory Pre-Bötzinger Complex Glutamatergic, Dbx1-Derived, and Somatostatin-Expressing Neuron Populations Revealed by Graded Optogenetic Inhibition

eNeuro ◽  
2016 ◽  
Vol 3 (3) ◽  
pp. ENEURO.0081-16.2016 ◽  
Author(s):  
Hidehiko Koizumi ◽  
Bryan Mosher ◽  
Mohammad F. Tariq ◽  
Ruli Zhang ◽  
Naohiro Koshiya ◽  
...  
Keyword(s):  
Neuron Populations ◽  
Bötzinger Complex ◽  
Voltage Dependent

DISTRIBUTION OF GABA TRANSPORTER (GAT1) LEVELS IN THE BÖTZINGER COMPLEX AT THE EARLY STAGES OF POSTNATAL DEVELOPMENT IN RATS WITH PRENATAL SEROTONIN DEFICIENCY

2020 ◽  
pp. 7-12
Author(s):  
Л. И. Хожай
Keyword(s):  
Postnatal Development ◽  
Tryptophan Hydroxylase ◽  
Polyclonal Antibodies ◽  
Gaba Transporter ◽  
Early Stages ◽  
Bötzinger Complex ◽  
Neuronal Processes ◽  
Serotonin Deficiency ◽  
Gaba Transporter 1 ◽  
Primary Rabbit

Цель работы - исследование распределения уровня GAT-транспортера ГАМК в комплексе Бетцингера на разных сроках раннего постнатального развития крыс в норме и при пренатальном дефиците серотонина. Материал и методы. Работа проведена на лабораторных крысах линии Wistar. Снижение уровня эндогенного серотонина в эмбриональный период осуществляли методом ингибирования триптофан-гидроксилазы пара-хлорфенилаланином (пХФА). Выявление транспортного белка GAТпроводили посредством иммуногистохимической реакции с использованием первичных кроличьих поликлональных антител anti-GABA transporter1 (AbCam, Великобритания). Мозг исследовали на 5-, 10-е и 20-е сутки постнатального развития. Результаты. В комплексе Бетцингера на ранних сроках постнатального развития у контрольных животных отмечено колебание уровня GAT-транспортера ГАМК. На 1-й неделе жизни уровень GATбыл высоким как в сети отростков и терминалей, так и в синапсах. В течение 2-й недели жизни уровень GATснижался, а к концу 3-й недели - повышался вновь, достигая исходного уровня. Дефицит серотонина в пренатальный период вызывал у подопытных животных существенное увеличение уровня GATв нейропиле комплекса Бетцингера на всех изученных сроках постнатального развития. Выводы. Пренатальный дефицит серотонина приводит к существенному повышению уровня GAT-транспортера ГАМК в ранние сроки постнатального развития, что может приводить к изменению трансмиссии ГАМК и, как следствие, к нарушению баланса тормозных и возбуждающих эффектов в дыхательном ядре. Objective - to study the distribution of GABA transporter 1 (GAT) levels in the Bötzinger complex at the early stages of postnatal development in rats with prenatal serotonin deficiency. Materials and methods. The work was carried out on Wistar line laboratory rats. To reduce the level of endogenous serotonin in the embryonic period, the method of tryptophan hydroxylase inhibition by para-chlorophenylalanine (PCPA) (Sigma, USA) was used. The GAT1 transport protein was detected by immunohistochemical reaction with anti-GABA transporter1 primary rabbit polyclonal antibodies (AbCam, UK). The brain was examined on the 5, 10 and 20 day of postnatal development. Results. At the early stages of postnatal development, a fluctuation in the GAT1 level of the GABA transporter was noted in the Bötzinger complex of control animals. In the first postnatal week, the GAT level was high both in the network of neuronal processes and terminals, and in synapses. During the 2 week of life, the GAT1 level decreased, and by the end of the 3 week it increased again, reaching the initial level. Deficiency of serotonin in the prenatal period caused a significant increase in the level of GAT in the neuropil of the Bötzinger complex in experimental animals at all studied stages of postnatal development. Conclusions. Prenatal deficiency of serotonin leads to a significant increase in the GAT1 level at the early stages of postnatal development, which can lead to a change in the GABA transmission, and, as a result, to a disturbance in the balance of inhibitory and stimulatory effects in the respiratory nuclei.

Glutamate Neurotransmission Is Not Required for, But May Modulate, Hypoxic Sensitivity of Pre-Bötzinger Complex In Vivo

2005 ◽  
Vol 93 (3) ◽  
pp. 1278-1284 ◽  
Author(s):  
Irene C. Solomon
Keyword(s):  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Glutamate Release ◽  
Receptor Activation ◽  
Motor Output ◽  
Induced Response ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Focal hypoxia in the pre-Bötzinger complex (pre-BötC) in vivo elicits excitation of inspiratory motor output by modifying the patterning and timing of phrenic bursts. Hypoxia, however, has been reported to enhance glutamate release in some regions of the brain, including the medullary ventral respiratory column; thus the pre-BötC–mediated hypoxic respiratory excitation may result from, or be influenced by, hypoxia-induced activation of ionotropic glutamate [i.e., excitatory amino acid (EAA)] receptors. To test this possibility, the effects of focal pre-BötC hypoxia [induced by sodium cyanide (NaCN)] were examined before and after blockade of ionotropic EAA receptors [using kynurenic acid (KYN)] in this region in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Before blockade of ionotropic EAA receptors, unilateral microinjection of NaCN (1 mM; 10–20 nl) into the pre-BötC produced either phasic or tonic excitation of phrenic nerve discharge. Unilateral microinjection of KYN (50–100 mM; 40 nl) decreased the amplitude and frequency of basal phrenic nerve discharge; however, subsequent microinjection of NaCN, but not dl-homocysteic acid (DLH, a glutamate analog), still produced excitation of phrenic motor output. Under these conditions, the NaCN-induced excitation included frequency modulation (FM) of phasic phrenic bursts, and in many cases, augmented and/or fractionated phrenic bursts. These findings show that the hypoxia-sensing function of the in vivo pre-BötC, which produces excitation of phrenic nerve discharge, is not dependent on activation of ionotropic glutamate receptors, but ionotropic glutamate receptor activation may modify the expression of the focal hypoxia-induced response. Thus these findings provide additional support to the concept of intrinsic hypoxic sensitivity of the pre-BötC.

Pre-Bötzinger Complex Functions as a Central Hypoxia Chemosensor for Respiration In Vivo

2000 ◽  
Vol 83 (5) ◽  
pp. 2854-2868 ◽  
Author(s):  
Irene C. Solomon ◽  
Norman H. Edelman ◽  
Judith A. Neubauer
Keyword(s):  
Short Duration ◽  
Phrenic Nerve ◽  
Excitatory Amino Acid ◽  
Respiratory Rhythm ◽  
High Amplitude ◽  
Unique Region ◽  
Homocysteic Acid ◽  
Bötzinger Complex ◽  
Nerve Discharge

Recently, we identified a region located in the pre-Bötzinger complex (pre-BötC; the proposed locus of respiratory rhythm generation) in which activation of ionotropic excitatory amino acid receptors usingdl-homocysteic acid (DLH) elicits a variety of excitatory responses in the phrenic neurogram, ranging from tonic firing to a rapid series of high-amplitude, rapid rate of rise, short-duration inspiratory bursts that are indistinguishable from gasps produced by severe systemic hypoxia. Therefore we hypothesized that this unique region is chemosensitive to hypoxia. To test this hypothesis, we examined the response to unilateral microinjection of sodium cyanide (NaCN) into the pre-BötC in chloralose- or chloralose/urethan-anesthetized vagotomized, paralyzed, mechanically ventilated cats. In all experiments, sites in the pre-BötC were functionally identified using DLH (10 mM, 21 nl) as we have previously described. All sites were histologically confirmed to be in the pre-BötC after completion of the experiment. Unilateral microinjection of NaCN (1 mM, 21 nl) into the pre-BötC produced excitation of phrenic nerve discharge in 49 of the 81 sites examined. This augmentation of inspiratory output exhibited one of the following changes in cycle timing and/or pattern: 1) a series of high-amplitude, short-duration bursts in the phrenic neurogram (a discharge similar to a gasp), 2) a tonic excitation of phrenic neurogram output, 3) augmented bursts in the phrenic neurogram (i.e., eupneic breath ending with a gasplike burst), or 4) an increase in frequency of phrenic bursts accompanied by small increases or decreases in the amplitude of integrated phrenic nerve discharge. Our findings identify a locus in the brain stem in which focal hypoxia augments respiratory output. We propose that the respiratory rhythm generator in the pre-BötC has intrinsic hypoxic chemosensitivity that may play a role in hypoxia-induced gasping.

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