scholarly journals NMDA receptors in preBötzinger complex neurons can drive respiratory rhythm independent of AMPA receptors

2007 ◽  
Vol 582 (1) ◽  
pp. 359-368 ◽  
Author(s):  
Consuelo Morgado-Valle ◽  
Jack L. Feldman
Keyword(s):  
Nmda Receptors ◽  
Ampa Receptors ◽  
Respiratory Rhythm ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

scholarly journals  4* Nicotinic Receptors in preBotzinger Complex Mediate Cholinergic/Nicotinic Modulation of Respiratory Rhythm

2008 ◽  
Vol 28 (2) ◽  
pp. 519-528 ◽  
Author(s):  
X. M. Shao ◽  
W. Tan ◽  
J. Xiu ◽  
N. Puskar ◽  
C. Fonck ◽  
...  
Keyword(s):  
Nicotinic Receptors ◽  
Respiratory Rhythm ◽  
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 Acetylcholine Modulates Respiratory Pattern: Effects Mediated by M3-Like Receptors in PreBötzinger Complex Inspiratory Neurons

2000 ◽  
Vol 83 (3) ◽  
pp. 1243-1252 ◽  
Author(s):  
X. M. Shao ◽  
J. L. Feldman
Keyword(s):  
Voltage Clamp ◽  
Respiratory Rhythm ◽  
Reversal Potential ◽  
Motor Output ◽  
Neonatal Rat ◽  
Inward Current ◽  
Inspiratory Neurons ◽  
Bath Application ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Perturbations of cholinergic neurotransmission in the brain stem affect respiratory motor pattern both in vivo and in vitro; the underlying cellular mechanisms are unclear. Using a medullary slice preparation from neonatal rat that spontaneously generates respiratory rhythm, we patch-clamped inspiratory neurons in the preBötzinger complex (preBötC), the hypothesized site for respiratory rhythm generation, and simultaneously recorded respiratory-related motor output from the hypoglossal nerve (XIIn). Most (88%) of the inspiratory neurons tested responded to local application of acetylcholine (ACh) or carbachol (CCh) or bath application of muscarine. Bath application of 50 μM muscarine increased the frequency, amplitude, and duration of XIIn inspiratory bursts. At the cellular level, muscarine induced a tonic inward current, increased the duration, and decreased the amplitude of the phasic inspiratory inward currents in preBötC inspiratory neurons recorded under voltage clamp at −60 mV. Muscarine also induced seizure-like activity evident during expiratory periods in XIIn activity; these effects were blocked by atropine. In the presence of tetrodotoxin (TTX), local ejection of 2 mM CCh or ACh onto preBötC inspiratory neurons induced an inward current along with an increase in membrane conductance under voltage clamp and induced a depolarization under current clamp. This response was blocked by atropine in a concentration-dependent manner. Bath application of 1 μM pirenzepine, 10 μM gallamine, or 10 μM himbacine had little effect on the CCh-induced current, whereas 10 μM 4-diphenylacetoxy- N-methylpiperidine methiodide blocked the current. The current-voltage ( I-V) relationship of the CCh-induced response was linear in the range of −110 to −20 mV and reversed at −11.4 mV. Similar responses were found in both pacemaker and nonpacemaker inspiratory neurons. The response to CCh was unaffected when patch electrodes contained a high concentration of EGTA (11 mM) or bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid (10 mM). The response to CCh was reduced greatly by substitution of 128 mM Tris-Cl for NaCl in the bath solution; the I-Vcurve shifted to the left and the reversal potential shifted to −47 mV. Lowering extracellular Cl−concentration from 140 to 70 mM had no effect on the reversal potential. These results suggest that in preBötC inspiratory neurons, ACh acts on M3-like ACh receptors on the postsynaptic neurons to open a channel permeable to Na+and K+that is not Ca2+dependent. This inward cation current plays a major role in depolarizing preBötC inspiratory neurons, including pacemakers, that may account for the ACh-induced increase in the frequency of respiratory motor output observed at the systems/behavioral level.

scholarly journals Putting the theory into 'burstlet theory': A biophysical model of bursts and burstlets in the respiratory preBötzinger complex

2021 ◽  
Author(s):  
Ryan S Phillips ◽  
Jonathan E Rubin
Keyword(s):  
Neuronal Activity ◽  
Respiratory Rhythm ◽  
Motor Output ◽  
Biophysical Model ◽  
Extracellular Potassium ◽  
Rhythm Generation ◽  
Cationic Current ◽  
Respiratory Rhythm Generation ◽  
Prebotzinger Complex ◽  
Prebötzinger Complex

Inspiratory breathing rhythms arise from synchronized neuronal activity in a bilaterally distributed brainstem structure known as the preBötzinger complex (preBötC). In in vitro slice preparations containing the preBötC, extracellular potassium must be elevated above physiological levels (to 7-9mM) to observe regular rhythmic respiratory motor output in the hypoglossal nerve to which the preBötC projects. Reexamination of how extracellular K+ affects preBötC neuronal activity has revealed that low amplitude oscillations persist at physiological levels. These oscillatory events are sub-threshold from the standpoint of transmission to motor output and are dubbed burstlets. Burstlets arise from synchronized neural activity in a rhythmogenic neuronal subpopulation within the preBötC that in some instances may fail to recruit the larger network events, or bursts, required to generate motor output. The fraction of subthreshold preBötC oscillatory events (burstlet fraction) decreases sigmoidally with increasing extracellular potassium. These observations underlie the burstlet theory of respiratory rhythm generation. Experimental and computational studies have suggested that recruitment of the non-rhythmogenic component of the preBötC population requires intracellular Ca2+ dynamics and activation of a calcium-activated non-selective cationic current. In this computational study, we show how intracellular calcium dynamics driven by synaptically triggered Ca2+ influx as well as Ca2+ release/uptake by the endoplasmic reticulum in conjunction with a calcium-activated non-selective cationic current can explain all of the key observations underlying the burstlet theory of respiratory rhythm generation. Thus, we provide a mechanistic basis to unify the experimental findings on rhythm generation and motor output recruitment in the preBötC.

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