Putting the theory into 'burstlet theory' with a biophysical model of burstlets and bursts in the respiratory preBötzinger complex
- University of Pittsburgh, United States
Abstract
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 reproduce and offer an explanation for many of the key properties associated with the burstlet theory of respiratory rhythm generation. Altogether, our modeling work provides a mechanistic basis that can unify a wide range of experimental findings on rhythm generation and motor output recruitment in the preBötC.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-8. Simulation code has been published on GitHub at the following link.https://github.com/RyanSeanPhillips/Putting-the-theory-into-burstlet-theory
Article and author information
Author details
Funding
National Science Foundation (DMS1951095)
- Jonathan E Rubin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Phillips & Rubin
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Putting the theory into 'burstlet theory' with a biophysical model of burstlets and bursts in the respiratory preBötzinger complex
eLife 11:e75713.
https://doi.org/10.7554/eLife.75713
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