scholarly journals Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model

2018 ◽  
Author(s):  
Ryan S. Phillips ◽  
Tibin T. John ◽  
Hidehiko Koizumi ◽  
Yaroslav I. Molkov ◽  
Jeffrey C. Smith
Keyword(s):  
Computational Model ◽  
Sodium Current ◽  
Data Driven ◽  
The Novel ◽  
Synaptic Connections ◽  
Rhythm Generation ◽  
Population Activity ◽  
Cationic Current ◽  
Bötzinger Complex ◽  
Synaptic Mechanisms

AbstractAn autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms—a persistent sodium current (INaP) and a calcium-activated non-selective cationic current (ICAN)—were proposed to individually or in combination generate cellular-and circuit-level oscillations, but their roles are debated without resolution. We re-examined these roles with a new computational model of an excitatory population with randomly distributed INaP and ICAN conductances and synaptic connections. This model robustly reproduces experimental data showing contrary to previous hypotheses, rhythm generation is independent of ICAN activation, which instead determines population activity amplitude. The novel insight is that this occurs when ICAN is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on INaP in a subpopulation forming the rhythmogenic kernel. The model explains how the rhythm and amplitude of respiratory oscillations involve distinct biophysical mechanisms.

scholarly journals Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Ryan S Phillips ◽  
Tibin T John ◽  
Hidehiko Koizumi ◽  
Yaroslav I Molkov ◽  
Jeffrey C Smith
Keyword(s):  
Sodium Current ◽  
Data Driven ◽  
Persistent Sodium Current ◽  
Rhythm Generation ◽  
Critical Component ◽  
Population Activity ◽  
Cationic Current ◽  
Bötzinger Complex ◽  
Excitatory Neurons ◽  
Synaptic Mechanisms

An autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms—a persistent sodium current (INaP) and a calcium-activated non-selective cationic current (ICAN)—were proposed to individually or in combination generate cellular- and circuit-level oscillations, but their roles are debated without resolution. We re-examined these roles in a model of a synaptically connected population of excitatory neurons with ICAN and INaP. This model robustly reproduces experimental data showing that rhythm generation can be independent of ICAN activation, which determines population activity amplitude. This occurs when ICAN is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on INaP in a subpopulation forming the rhythmogenic kernel. The model explains how the rhythm and amplitude of respiratory oscillations involve distinct biophysical mechanisms.

Isolation of the Kernel for Respiratory Rhythm Generation in a Novel Preparation: The Pre-Bötzinger Complex “Island”

2001 ◽  
Vol 85 (4) ◽  
pp. 1772-1776 ◽  
Author(s):  
Shereé M. Johnson ◽  
Naohiro Koshiya ◽  
Jeffrey C. Smith
Keyword(s):  
Respiratory Rhythm ◽  
Fluorescent Imaging ◽  
Extracellular Potassium ◽  
Synaptic Inhibition ◽  
Rhythm Generation ◽  
Population Activity ◽  
Thin Slices ◽  
Bötzinger Complex ◽  
Population Burst ◽  
Respiratory Rhythm Generation

The pre-Bötzinger complex (pre-BötC), a bilaterally distributed network of rhythmogenic neurons within the ventrolateral medulla, has been proposed to be the critical locus for respiratory rhythm generation in mammals. To date, thin transverse medullary slice preparations that capture the pre-BötC have served as the optimal experimental model to study the region's inherent cellular and network properties. We have reduced the thin slices to isolated pre-BötC “islands” to further establish whether the pre-BötC has intrinsic rhythmicity and is the kernel for rhythmogenesis in the slice. We recorded neuron population activity locally in the pre-BötC with macroelectrodes and fluorescent imaging of Ca2+ activities with Calcium Green-1AM dye before and after excising the island. The isolated island remained rhythmically active with a population burst profile similar to the inspiratory burst in the slice. Rhythmic population activity persisted in islands after block of GABAAergic and glycinergic synaptic inhibition. The loci of pre-BötC Ca2+ activity imaged in thin slices and islands were similar, and imaged pre-BötC neurons exhibited synchronized flashing after blocking synaptic inhibition. Population burst frequency increased monotonically as extracellular potassium concentration was elevated, consistent with mathematical models consisting entirely of an excitatory network of synaptically coupled pacemaker neurons with heterogeneous, voltage-dependent bursting properties. Our results provide further evidence for a rhythmogenic kernel in the pre-BötC in vitro and demonstrate that the islands are ideal preparations for studying the kernel's intrinsic properties.

The Healing Magic of Joy: Understanding Magic as a Metaphor for Positive Emotion in The Secret Garden

2015 ◽  
Vol 8 (2) ◽  
pp. 127-141
Author(s):  
Margrete Lamond
Keyword(s):  
Positive Affect ◽  
Scientific Method ◽  
Positive Emotion ◽  
Literary Analysis ◽  
Data Driven ◽  
The Novel ◽  
Top Down ◽  
Affective Content ◽  
The Secret Garden ◽  
Biological Nature

Literary analysis tends to be conceptual and top-down driven. Data-driven analysis, although it belongs more to the domain of scientific method, can nevertheless sometimes reveal elements of narrative that conceptual readings may fall short of identifying. In critiques of Burnett's The Secret Garden, the children's return to health is generally understood to be the result of their interactions with nature. Some readings add the power of storytelling as a healing force in the novel. Burnett's concept of magic has tended to be treated with uneasy abstractions, and the influence of affect on health remains open for further investigation. This article bases its argument on data-driven analysis that charts how affective content in the novel occurs in conjunction with references to magic. It identifies the narrative significance of negative allusions to nature and how concepts of magic occur alongside representations of positive affect, and suggests that the magic of healing in The Secret Garden is not the transforming power of biological nature, nor the transforming power of storytelling, but the transforming power of surprise, wonder and happiness in conjunction with all these factors. Positive affect represents the essence of what Burnett means by magic.

Sodium Currents in Neurons From the Rostroventrolateral Medulla of the Rat

2003 ◽  
Vol 90 (3) ◽  
pp. 1635-1642 ◽  
Author(s):  
Ilya A. Rybak ◽  
Krzysztof Ptak ◽  
Natalia A. Shevtsova ◽  
Donald R. McCrimmon
Keyword(s):  
Sodium Channels ◽  
Sodium Current ◽  
Cell Voltage ◽  
Kinetic Properties ◽  
Persistent Sodium Current ◽  
Sodium Currents ◽  
Bötzinger Complex ◽  
Window Current ◽  
Bursting Activity

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15). Neurons were investigated using the whole cell voltage-clamp technique. Standard activation and inactivation protocols were used to characterize the steady-state and kinetic properties of the rapidly inactivating sodium current. Slow depolarizing ramp protocols were used to characterize the noninactivating sodium current. The “window” component of the rapidly inactivating sodium current was calculated using mathematical modeling. The persistent sodium current was revealed by subtraction of the window current from the total noninactivating sodium current. Our results provide evidence of the presence of persistent sodium currents in neurons of the rat rostroventrolateral medulla and determine voltage-gated characteristics of activation and inactivation of rapidly inactivating and persistent sodium channels in these neurons.

Data-driven tracking consensus for a class of unknown nonlinear multi-agent systems

2021 ◽  
pp. 107754632110340
Author(s):  
Jia Wu ◽  
Ning Liu ◽  
Wenyan Tang
Keyword(s):  
Control Method ◽  
Sufficient Conditions ◽  
Data Driven ◽  
The Novel ◽  
Multi Agent Systems ◽  
Tracking Errors ◽  
Agent Systems ◽  
Model Free ◽  
Strongly Connected ◽  
Multi Agent

This study investigates the tracking consensus problem for a class of unknown nonlinear multi-agent systems A novel data-driven protocol for this problem is proposed by using the model-free adaptive control method To obtain faster convergence speed, one-step-ahead desired signal is introduced to construct the novel protocol Here, switching communication topology is considered, which is not required to be strongly connected all the time Through rigorous analysis, sufficient conditions are given to guarantee that the tracking errors of all agents are convergent under the novel protocol Examples are given to validate the effectiveness of results derived in this article

Models of Respiratory Rhythm Generation in the Pre-Bötzinger Complex. I. Bursting Pacemaker Neurons

1999 ◽  
Vol 82 (1) ◽  
pp. 382-397 ◽  
Author(s):  
Robert J. Butera ◽  
John Rinzel ◽  
Jeffrey C. Smith
Keyword(s):  
Membrane Potential ◽  
Respiratory Rhythm ◽  
Rhythm Generation ◽  
Minimal Models ◽  
Dynamic Features ◽  
Bursting Neurons ◽  
Wide Range ◽  
Bötzinger Complex ◽  
Voltage Dependent ◽  
Respiratory Rhythm Generation

A network of oscillatory bursting neurons with excitatory coupling is hypothesized to define the primary kernel for respiratory rhythm generation in the pre-Bötzinger complex (pre-BötC) in mammals. Two minimal models of these neurons are proposed. In model 1, bursting arises via fast activation and slow inactivation of a persistent Na+ current I NaP-h. In model 2, bursting arises via a fast-activating persistent Na+ current INaP and slow activation of a K+ current IKS. In both models, action potentials are generated via fast Na+ and K+currents. The two models have few differences in parameters to facilitate a rigorous comparison of the two different burst-generating mechanisms. Both models are consistent with many of the dynamic features of electrophysiological recordings from pre-BötC oscillatory bursting neurons in vitro, including voltage-dependent activity modes (silence, bursting, and beating), a voltage-dependent burst frequency that can vary from 0.05 to >1 Hz, and a decaying spike frequency during bursting. These results are robust and persist across a wide range of parameter values for both models. However, the dynamics of model 1 are more consistent with experimental data in that the burst duration decreases as the baseline membrane potential is depolarized and the model has a relatively flat membrane potential trajectory during the interburst interval. We propose several experimental tests to demonstrate the validity of either model and to differentiate between the two mechanisms.

scholarly journals SARS2020: an integrated platform for identification of novel coronavirus by a consensus sequence-function model

2020 ◽  
Author(s):  
Dachuan Zhang ◽  
Tong Zhang ◽  
Sheng Liu ◽  
Dandan Sun ◽  
Shaozhen Ding ◽  
...  
Keyword(s):  
Biological Function ◽  
Consensus Sequence ◽  
Rapid Identification ◽  
Data Driven ◽  
Supplementary Information ◽  
Respiratory Syndrome Virus ◽  
The Novel ◽  
Function Model ◽  
Catalytic Function ◽  
Novel Coronavirus

Abstract Motivation The 2019 novel coronavirus outbreak has significantly affected global health and society. Thus, predicting biological function from pathogen sequence is crucial and urgently needed. However, little work has been conducted to identify viruses by the enzymes that they encode, and which are key to pathogen propagation. Results We built a comprehensive scientific resource, SARS2020, which integrates coronavirus-related research, genomic sequences and results of anti-viral drug trials. In addition, we built a consensus sequence-catalytic function model from which we identified the novel coronavirus as encoding the same proteinase as the severe acute respiratory syndrome virus. This data-driven sequence-based strategy will enable rapid identification of agents responsible for future epidemics. Availabilityand implementation SARS2020 is available at http://design.rxnfinder.org/sars2020/. Supplementary information Supplementary data are available at Bioinformatics online.

Respiratory rhythm generation during gasping depends on persistent sodium current

2006 ◽  
Vol 9 (3) ◽  
pp. 311-313 ◽  
Author(s):  
Julian F R Paton ◽  
Ana P L Abdala ◽  
Hidehiko Koizumi ◽  
Jeffrey C Smith ◽  
Walter M St-John
Keyword(s):  
Sodium Current ◽  
Respiratory Rhythm ◽  
Persistent Sodium Current ◽  
Rhythm Generation ◽  
Respiratory Rhythm Generation
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