scholarly journals Phase‐ and state‐dependent modulation of breathing pattern by preBötzinger complex somatostatin expressing neurons

2021 ◽  
Author(s):  
Raquel P. Sousa Abreu ◽  
Evgeny Bondarenko ◽  
Jack L. Feldman
Keyword(s):  
Breathing Pattern ◽  
State Dependent ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Phase- and State-Dependent Modulation of Breathing Pattern by preBötzinger Complex Somatostatin Expressing Neurons

2021 ◽  
Author(s):  
Raquel P. de Sousa Abreu ◽  
Evgeny Bondarenko ◽  
Jack L. Feldman
Keyword(s):  
Breathing Pattern ◽  
Pattern Generation ◽  
Respiratory Pattern ◽  
Phase Advance ◽  
Breathing Frequency ◽  
State Dependent ◽  
Freely Behaving ◽  
Freely Moving ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

AbstractAs neuronal subtypes are increasingly categorized, delineating their functional role is paramount. The preBötzinger Complex (preBötC) subpopulation expressing the neuropeptide somatostatin (SST) is classified as mostly excitatory, inspiratory-modulated and not rhythmogenic. We further characterized their phenotypic identity; 87% were glutamatergic and the balance were glycinergic and/or GABAergic. We then used optogenetics to investigate their modulatory role in both anesthetized and freely moving mice. In anesthetized mice, short photostimulation (100 ms) of preBötC SST+ neurons modulated breathing-related variables in a combinatory phase- and state-dependent manner; changes in inspiratory duration, inspiratory peak amplitude (Amp), and phase were different at higher (≥2.5 Hz) vs. lower (<2.5 Hz) breathing frequency. Moreover, we observed a biphasic effect of photostimulation during expiration that is probabilistic, i.e., photostimulation given at the same phase in consecutive cycles can evoke opposite responses (lengthening vs. shortening of the phase). This unexpected probabilistic state- and phase-dependent responses to photostimulation exposed properties of the preBötC that were not predicted and cannot be readily accounted for in current models of preBötC pattern generation. In freely moving mice, prolonged photostimulation decreased f in normoxia, hypoxia, or hypercapnia, and increased Amp and produced a phase advance, which was similar to the results in anesthetized mice when f≥2.5 Hz. We conclude that preBötC SST+ neurons are a key mediator of the extraordinary and essential lability of breathing pattern.Key points summaryWe transfected preBötzinger Complex (preBötC) somatostatin-expressing (SST+) neurons, which modulate respiratory pattern, but are not rhythmogenic, with channelrhodopsin to investigate phase- and state-dependent modulation of breathing pattern in anesthetized and freely behaving mice in normoxia, hypoxia, and hypercapnia.In anesthetized mice, photostimulation of preBötC SST+ neurons during inspiration increased inspiratory duration and amplitude regardless of baseline breathing frequency, f.In anesthetized mice with low f (<2.5 Hz), photostimulation of preBötC SST+ neurons during expiration evoked either phase advance or phase delay, whereas in anesthetized mice with high f (≥2.5 Hz) and in freely behaving mice in normoxia, hypoxia, or hypercapnia, photostimulation always evoked phase advance.Phase- and state-dependency is a function of overall breathing network excitability.The f-dependent probabilistic modulation of breathing pattern by preBötC SST+ neurons was unexpected, requiring reconsideration of current models of preBötC function, which neither predict nor can readily account for such responses.

scholarly journals ATP sensitivity of preBötzinger complex neurones in neonatal ratin vitro: mechanism underlying a P2 receptor-mediated increase in inspiratory frequency

2008 ◽  
Vol 586 (5) ◽  
pp. 1429-1446 ◽  
Author(s):  
A. R. Lorier ◽  
J. Lipski ◽  
G. D. Housley ◽  
J. J. Greer ◽  
G. D. Funk
Keyword(s):  
P2 Receptor ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Neural mechanisms underlying respiratory regulation within the preBötzinger complex of the rabbit

2021 ◽  
pp. 103736
Author(s):  
Elenia Cinelli ◽  
Donatella Mutolo ◽  
Tito Pantaleo ◽  
Fulvia Bongianni
Keyword(s):  
Neural Mechanisms ◽  
Respiratory Regulation ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons

2001 ◽  
Vol 4 (9) ◽  
pp. 927-930 ◽  
Author(s):  
Paul A. Gray ◽  
Wiktor A. Janczewski ◽  
Nicholas Mellen ◽  
Donald R. McCrimmon ◽  
Jack L. Feldman
Keyword(s):  
Neurokinin 1 Receptor ◽  
Normal Breathing ◽  
Neurokinin 1 ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

cAMP‐dependent modulation of I h underlies the P2Y 1 receptor‐mediated excitation of the preBötzinger Complex inspiratory network in vitro

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Yong Zhang ◽  
Vivian Biancardi ◽  
Ana Miranda Tapia ◽  
Toka Abu Jaib ◽  
Alexander Gourine ◽  
...  
Keyword(s):  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Mechanisms Underlying Regulation of Respiratory Pattern by Nicotine in PreBötzinger Complex

2001 ◽  
Vol 85 (6) ◽  
pp. 2461-2467 ◽  
Author(s):  
Xuesi M. Shao ◽  
Jack L. Feldman
Keyword(s):  
Respiratory Frequency ◽  
Neonatal Rat ◽  
Respiratory Pattern ◽  
Dependent Manner ◽  
Baseline Noise ◽  
Arterial Blood ◽  
Inspiratory Neurons ◽  
Excitatory Neurotransmission ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Cholinergic neurotransmission plays a role in regulation of respiratory pattern. Nicotine from cigarette smoke affects respiration and is a risk factor for sudden infant death syndrome (SIDS) and sleep-disordered breathing. The cellular and synaptic mechanisms underlying this regulation are not understood. Using a medullary slice preparation from neonatal rat that contains the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythm generation, and generates respiratory-related rhythm in vitro, we examined the effects of nicotine on excitatory neurotransmission affecting inspiratory neurons in preBötC and on the respiratory-related motor activity from hypoglossal nerve (XIIn). Microinjection of nicotine into preBötC increased respiratory frequency and decreased the amplitude of inspiratory bursts, whereas when injected into XII nucleus induced a tonic activity and an increase in amplitude but not in frequency of inspiratory bursts from XIIn. Bath application of nicotine (0.2–0.5 μM, approximately the arterial blood nicotine concentration immediately after smoking a cigarette) increased respiratory frequency up to 280% of control in a concentration-dependent manner. Nicotine decreased the amplitude to 82% and increased the duration to 124% of XIIn inspiratory bursts. In voltage-clamped preBötC inspiratory neurons (including neurons with pacemaker properties), nicotine induced a tonic inward current of −19.4 ± 13.4 pA associated with an increase in baseline noise. Spontaneous excitatory postsynaptic currents (sEPSCs) present during the expiratory period increased in frequency to 176% and in amplitude to 117% of control values; the phasic inspiratory drive inward currents decreased in amplitude to 66% and in duration to 89% of control values. The effects of nicotine were blocked by mecamylamine (Meca). The inspiratory drive current and sEPSCs were completely eliminated by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the presence or absence of nicotine. In the presence of tetrodotoxin (TTX), low concentrations of nicotine did not induce any tonic current or any increase in baseline noise, nor affect the input resistance in inspiratory neurons. In this study, we demonstrated that nicotine increased respiratory frequency and regulated respiratory pattern by modulating the excitatory neurotransmission in preBötC. Activation of nicotinic acetylcholine receptors (nAChRs) enhanced the tonic excitatory synaptic input to inspiratory neurons including pacemaker neurons and at the same time, inhibited the phasic excitatory coupling between these neurons. These mechanisms may account for the cholinergic regulation of respiratory frequency and pattern.

scholarly journals Exploring opioid receptor dependent biased agonism in the PreBötzinger Complex

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Caroline C. Szujewski ◽  
Chrishon Campbell ◽  
Alfredo J. Garcia
Keyword(s):  
Opioid Receptor ◽  
Biased Agonism ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Neuronal Mediators of the Frequency Increase Evoked by Activation of P2Y 1 Receptors in the preBötzinger Complex Inspiratory Rhythm Generating Network in Vitro

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Ana Miranda Tapia ◽  
Vivian Biancardi ◽  
Robert Reklow ◽  
Wei Zhang ◽  
Vladimir Rancic ◽  
...  
Keyword(s):  
Frequency Increase ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Muscarinic Modulation of Morphologically Identified Glycinergic Neurons in the Mouse PreBötzinger Complex

2020 ◽  
Vol 13 ◽  
Author(s):  
Fang Zheng ◽  
Barbara E. Nixdorf-Bergweiler ◽  
Elke Edelmann ◽  
Johannes F. M. van Brederode ◽  
Christian Alzheimer
Keyword(s):  
Prebotzinger Complex ◽  
Prebötzinger Complex ◽  
Muscarinic Modulation
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