scholarly journals Defining preBötzinger Complex Rhythm- and Pattern-Generating Neural Microcircuits In Vivo

Neuron ◽  
2016 ◽  
Vol 91 (3) ◽  
pp. 602-614 ◽  
Author(s):  
Yan Cui ◽  
Kaiwen Kam ◽  
David Sherman ◽  
Wiktor A. Janczewski ◽  
Yu Zheng ◽  
...  
Keyword(s):  
Prebotzinger Complex ◽  
Prebötzinger Complex

Vagal Feedback Obscures the Effects of Systemic Opioids on Respiratory Rate in the preBötzinger Complex in Young Rabbits in vivo

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Astrid G. Stucke ◽  
Barbara Palkovic ◽  
Jennifer J. Callison ◽  
Vitaliy Marchenko ◽  
Eckehard A.E. Stuth ◽  
...  
Keyword(s):  
Respiratory Rate ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals Inspiratory Off-Switch Mediated by Optogenetic Activation of Inhibitory Neurons in the preBötzinger Complex In Vivo

2021 ◽  
Vol 22 (4) ◽  
pp. 2019
Author(s):  
Swen Hülsmann ◽  
Liya Hagos ◽  
Volker Eulenburg ◽  
Johannes Hirrlinger
Keyword(s):  
Respiratory Rate ◽  
Respiratory Rhythm ◽  
Inhibitory Neurons ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Transgenic Mouse Line ◽  
Respiratory Network ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

The role of inhibitory neurons in the respiratory network is a matter of ongoing debate. Conflicting and contradicting results are manifold and the question whether inhibitory neurons are essential for the generation of the respiratory rhythm as such is controversial. Inhibitory neurons are required in pulmonary reflexes for adapting the activity of the central respiratory network to the status of the lung and it is hypothesized that glycinergic neurons mediate the inspiratory off-switch. Over the years, optogenetic tools have been developed that allow for cell-specific activation of subsets of neurons in vitro and in vivo. In this study, we aimed to identify the effect of activation of inhibitory neurons in vivo. Here, we used a conditional transgenic mouse line that expresses Channelrhodopsin 2 in inhibitory neurons. A 200 µm multimode optical fiber ferrule was implanted in adult mice using stereotaxic surgery, allowing us to stimulate inhibitory, respiratory neurons within the core excitatory network in the preBötzinger complex of the ventrolateral medulla. We show that, in anesthetized mice, activation of inhibitory neurons by blue light (470 nm) continuously or with stimulation frequencies above 10 Hz results in a significant reduction of the respiratory rate, in some cases leading to complete cessation of breathing. However, a lower stimulation frequency (4–5 Hz) could induce a significant increase in the respiratory rate. This phenomenon can be explained by the resetting of the respiratory cycle, since stimulation during inspiration shortened the associated breath and thereby increased the respiratory rate, while stimulation during the expiratory interval reduced the respiratory rate. Taken together, these results support the concept that activation of inhibitory neurons mediates phase-switching by inhibiting excitatory rhythmogenic neurons in the preBötzinger complex.

scholarly journals Opioid-induced Respiratory Depression Is Only Partially Mediated by the preBötzinger Complex in Young and Adult Rabbits In Vivo

2015 ◽  
Vol 122 (6) ◽  
pp. 1288-1298 ◽  
Author(s):  
Astrid G. Stucke ◽  
Justin R. Miller ◽  
Ivana Prkic ◽  
Edward J. Zuperku ◽  
Francis A. Hopp ◽  
...  
Keyword(s):  
Respiratory Rate ◽  
Respiratory Depression ◽  
Respiratory Rhythm ◽  
Respiratory Drive ◽  
Phase Duration ◽  
Homocysteic Acid ◽  
Opioid Receptor Agonist ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Abstract Background: The preBötzinger Complex (preBC) plays an important role in respiratory rhythm generation. This study was designed to determine whether the preBC mediated opioid-induced respiratory rate depression at clinically relevant opioid concentrations in vivo and whether this role was age dependent. Methods: Studies were performed in 22 young and 32 adult New Zealand White rabbits. Animals were anesthetized, mechanically ventilated, and decerebrated. The preBC was identified by the tachypneic response to injection of d,l-homocysteic acid. (1) The μ-opioid receptor agonist [d-Ala2,N-Me-Phe4,Gly-ol]-enkephalin (DAMGO, 100 μM) was microinjected into the bilateral preBC and reversed with naloxone (1 mM) injection into the preBC. (2) Respiratory depression was achieved with intravenous remifentanil (0.08 to 0.5 μg kg−1 min−1). Naloxone (1 mM) was microinjected into the preBC in an attempt to reverse the respiratory depression. Results: (1) DAMGO injection depressed respiratory rate by 6 ± 8 breaths/min in young and adult rabbits (mean ± SD, P < 0.001). DAMGO shortened the inspiratory and lengthened the expiratory fraction of the respiratory cycle by 0.24 ± 0.2 in adult and young animals (P < 0.001). (2) During intravenous remifentanil infusion, local injection of naloxone into the preBC partially reversed the decrease in inspiratory fraction/increase in expiratory fraction in young and adult animals (0.14 ± 0.14, P < 0.001), but not the depression of respiratory rate (P = 0.19). PreBC injections did not affect respiratory drive. In adult rabbits, the contribution of non-preBC inputs to expiratory phase duration was larger than preBC inputs (3.5 [−5.2 to 1.1], median [25 to 75%], P = 0.04). Conclusions: Systemic opioid effects on respiratory phase timing can be partially reversed in the preBC without reversing the depression of respiratory rate.

scholarly journals PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Clément Menuet ◽  
Angela A Connelly ◽  
Jaspreet K Bassi ◽  
Mariana R Melo ◽  
Sheng Le ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Respiratory Neurons ◽  
Neuron Activity ◽  
Neuronal Tracing ◽  
Cardiovascular Neurons ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated.

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.

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