Modeling Insights into Potential Mechanisms of Opioid-Induced Respiratory Depression within Medullary and Pontine Networks DOI Creative Commons
Wendy L. Olsen, John A. Hayes,

Dale Shuman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

The opioid epidemic is a pervasive health issue and continues to have drastic impact on the United States. This primarily because opioids cause respiratory suppression leading of death in overdose failure (i.e., opioid-induced depression, OIRD). Opioid administration can affect frequency magnitude inspiratory motor drive by activating μ-opioid receptors that are located throughout control network brainstem. significantly ventilation blunt CO2 responsiveness, but precise neural mechanisms suppress breathing not fully understood. Previous research has suggested medullary pontine neuron activity disrupting upstream elements within this circuit. Inspiratory neurons exhibit synchrony consistent with shared excitation from other populations recurrent mechanisms. One possible target for excitatory synapses. Reduced excitability these synaptic may result disfacilitation reduced among neurons. Downstream effects abnormal output phrenic motoneurons resulting distressed breathing. We tested plausibility hypothesis computational model targeting fictive populations. conductances were systematically decreased while monitoring overall pattern aggregate firing rates subsets cell Simulations suggest highly selective, rather than generalized, actions synapses account different observed mechanics.

Language: Английский

Interdependence of cellular and network properties in respiratory rhythm generation DOI Creative Commons
Ryan S. Phillips, Nathan A. Baertsch

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(19)

Published: May 1, 2024

How breathing is generated by the preBötzinger complex (preBötC) remains divided between two ideological frameworks, and a persistent sodium current (I

Language: Английский

Citations

4
The multifunctionality of the brainstem breathing control circuit DOI Creative Commons
Kevin Yackle, Jeehaeh Do

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 90, P. 102974 - 102974

Published: Jan. 28, 2025

Subconscious breathing is generated by a network of brainstem nodes with varying purposes, like pacing or patterning certain breath phase. Decades anatomy, pharmacology, and physiology studies have identified characterized the system's fundamental properties that produce robust breathing, we now well-conceived computational models are based on detailed descriptions neuronal connectivity, biophysical properties, functions in breathing. In total, considerable understanding control circuit. But, last five years, utilization molecular genetic approaches to study neural subtypes within each node has led new era circuit research explains how integrated more complex behaviors speaking running connected other physiological systems our state-of-mind. This review will describe basic role key components then highlight transformative discoveries broaden these brain areas. These serve illustrate creativity exciting future research.

Language: Английский

Citations

0
A novel mechanism for ramping bursts based on slow negative feedback in model respiratory neurons DOI
Sushmita Rose John, Ryan S. Phillips, Jonathan Rubin

et al.

Chaos An Interdisciplinary Journal of Nonlinear Science, Journal Year: 2024, Volume and Issue: 34(6)

Published: June 1, 2024

Recordings from pre-Bötzinger complex neurons responsible for the inspiratory phase of respiratory rhythm reveal a ramping burst pattern, starting around time that transition expiration to inspiration begins, in which spike rate gradually rises until into high-frequency occurs. The increase along is accompanied by gradual depolarization plateau potential underlies spikes. These effects may be functionally important inducing onset and hence maintaining effective respiration; however, most mathematical models bursting do not capture this activity pattern. Here, we study how modulation height afterhyperpolarization via slow inactivation an inward current can support various patterns including bursts. We use dynamical systems methods designed multiple timescale systems, such as bifurcation analysis based on decomposition averaging over fast oscillations, generate understanding predictions about specific dynamic lead also analyze transitions between other occur with parameter changes, could associated experimental manipulations, environmental conditions, and/or development.

Language: Английский

Citations

1
Modeling Insights into Potential Mechanisms of Opioid-Induced Respiratory Depression within Medullary and Pontine Networks DOI Creative Commons
Wendy L. Olsen, John A. Hayes,

Dale Shuman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

The opioid epidemic is a pervasive health issue and continues to have drastic impact on the United States. This primarily because opioids cause respiratory suppression leading of death in overdose failure (i.e., opioid-induced depression, OIRD). Opioid administration can affect frequency magnitude inspiratory motor drive by activating μ-opioid receptors that are located throughout control network brainstem. significantly ventilation blunt CO2 responsiveness, but precise neural mechanisms suppress breathing not fully understood. Previous research has suggested medullary pontine neuron activity disrupting upstream elements within this circuit. Inspiratory neurons exhibit synchrony consistent with shared excitation from other populations recurrent mechanisms. One possible target for excitatory synapses. Reduced excitability these synaptic may result disfacilitation reduced among neurons. Downstream effects abnormal output phrenic motoneurons resulting distressed breathing. We tested plausibility hypothesis computational model targeting fictive populations. conductances were systematically decreased while monitoring overall pattern aggregate firing rates subsets cell Simulations suggest highly selective, rather than generalized, actions synapses account different observed mechanics.

Language: Английский

Citations

0