Dataset Information

Robust concentration and frequency control in oscillatory homeostats.

ABSTRACT: Homeostatic and adaptive control mechanisms are essential for keeping organisms structurally and functionally stable. Integral feedback is a control theoretic concept which has long been known to keep a controlled variable A robustly (i.e. perturbation-independent) at a given set-point A(set) by feeding the integrated error back into the process that generates A. The classical concept of homeostasis as robust regulation within narrow limits is often considered as unsatisfactory and even incompatible with many biological systems which show sustained oscillations, such as circadian rhythms and oscillatory calcium signaling. Nevertheless, there are many similarities between the biological processes which participate in oscillatory mechanisms and classical homeostatic (non-oscillatory) mechanisms. We have investigated whether biological oscillators can show robust homeostatic and adaptive behaviors, and this paper is an attempt to extend the homeostatic concept to include oscillatory conditions. Based on our previously published kinetic conditions on how to generate biochemical models with robust homeostasis we found two properties, which appear to be of general interest concerning oscillatory and homeostatic controlled biological systems. The first one is the ability of these oscillators ("oscillatory homeostats") to keep the average level of a controlled variable at a defined set-point by involving compensatory changes in frequency and/or amplitude. The second property is the ability to keep the period/frequency of the oscillator tuned within a certain well-defined range. In this paper we highlight mechanisms that lead to these two properties. The biological applications of these findings are discussed using three examples, the homeostatic aspects during oscillatory calcium and p53 signaling, and the involvement of circadian rhythms in homeostatic regulation.

SUBMITTER: Thorsen K

PROVIDER: S-EPMC4169565 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Robust concentration and frequency control in oscillatory homeostats.

Thorsen Kristian K Agafonov Oleg O Selstø Christina H CH Jolma Ingunn W IW Ni Xiao Y XY Drengstig Tormod T Ruoff Peter P

PloS one 20140919 9

Homeostatic and adaptive control mechanisms are essential for keeping organisms structurally and functionally stable. Integral feedback is a control theoretic concept which has long been known to keep a controlled variable A robustly (i.e. perturbation-independent) at a given set-point A(set) by feeding the integrated error back into the process that generates A. The classical concept of homeostasis as robust regulation within narrow limits is often considered as unsatisfactory and even incompat ...[more]

PMID: 25238410

Similar Datasets

Project description:BACKGROUND: Constructing predictive dynamic models of interacting signalling networks remains one of the great challenges facing systems biology. While detailed dynamical data exists about individual pathways, the task of combining such data without further lengthy experimentation is highly nontrivial. The communicating links between pathways, implicitly assumed to be unimportant and thus excluded, are precisely what become important in the larger system and must be reinstated. To maintain the delicate phase relationships between signals, signalling networks demand accurate dynamical parameters, but parameters optimised in isolation and under varying conditions are unlikely to remain optimal when combined. The computational burden of estimating parameters increases exponentially with increasing system size, so it is crucial to find precise and efficient ways of measuring the behaviour of systems, in order to re-use existing work. RESULTS: Motivated by the above, we present a new frequency domain-based systematic analysis technique that attempts to address the challenge of network assembly by defining a rigorous means to quantify the behaviour of stochastic systems. As our focus we construct a novel coupled oscillatory model of p53, NF-kB and the mammalian cell cycle, based on recent experimentally verified mathematical models. Informed by online databases of protein networks and interactions, we distilled their key elements into simplified models containing the most significant parts. Having coupled these systems, we constructed stochastic models for use in our frequency domain analysis. We used our new technique to investigate the crosstalk between the components of our model and measure the efficacy of certain network-based heuristic measures. CONCLUSIONS: We find that the interactions between the networks we study are highly complex and not intuitive: (i) points of maximum perturbation do not necessarily correspond to points of maximum proximity to influence; (ii) increased coupling strength does not necessarily increase perturbation; (iii) different perturbations do not necessarily sum and (iv) overall, susceptibility to perturbation is amplitude and frequency dependent and cannot easily be predicted by heuristic measures.Our methodology is particularly relevant for oscillatory systems, though not limited to these, and is most revealing when applied to the results of stochastic simulation. The technique is able to characterise precisely the distance in behaviour between different models, different systems and different parts within the same system. It can also measure the difference between different simulation algorithms used on the same system and can be used to inform the choice of dynamic parameters. By measuring crosstalk between subsystems it can also indicate mechanisms by which such systems may be controlled in experiments and therapeutics. We have thus found our technique of frequency domain analysis to be a valuable benchmark systems-biological tool.

Project description:The nonsinusoidal waveform is emerging as an important feature of neuronal oscillations. However, the role of single-cycle shape dynamics in rapidly unfolding brain activity remains unclear. Here, we develop an analytical framework that isolates oscillatory signals from time series using masked empirical mode decomposition to quantify dynamical changes in the shape of individual cycles (along with amplitude, frequency, and phase) with instantaneous frequency. We show how phase-alignment, a process of projecting cycles into a regularly sampled phase grid space, makes it possible to compare cycles of different durations and shapes. "Normalized shapes" can then be constructed with high temporal detail while accounting for differences in both duration and amplitude. We find that the instantaneous frequency tracks nonsinusoidal shapes in both simulated and real data. Notably, in local field potential recordings of mouse hippocampal CA1, we find that theta oscillations have a stereotyped slow-descending slope in the cycle-wise average yet exhibit high variability on a cycle-by-cycle basis. We show how principal component analysis allows identification of motifs of theta cycle waveform that have distinct associations to cycle amplitude, cycle duration, and animal movement speed. By allowing investigation into oscillation shape at high temporal resolution, this analytical framework will open new lines of inquiry into how neuronal oscillations support moment-by-moment information processing and integration in brain networks.NEW & NOTEWORTHY We propose a novel analysis approach quantifying nonsinusoidal waveform shape. The approach isolates oscillations with empirical mode decomposition before waveform shape is quantified using phase-aligned instantaneous frequency. This characterizes the full shape profile of individual cycles while accounting for between-cycle differences in duration, amplitude, and timing. We validated in simulations before applying to identify a range of data-driven nonsinusoidal shape motifs in hippocampal theta oscillations.

Project description:IntroductionIt is unknown how the brain coordinates decisions to withstand personal costs in order to prevent other individuals' distress. Here we test whether local field potential (LFP) oscillations between brain regions create "neural contexts" that select specific brain functions and encode the outcomes of these types of intersubjective decisions.MethodsRats participated in an "Intersubjective Avoidance Test" (IAT) that tested rats' willingness to enter an innately aversive chamber to prevent another rat from getting shocked. c-Fos immunoreactivity was used to screen for brain regions involved in IAT performance. Multi-site local field potential (LFP) recordings were collected simultaneously and bilaterally from five brain regions implicated in the c-Fos studies while rats made decisions in the IAT. Local field potential recordings were analyzed using an elastic net penalized regression framework.ResultsRats voluntarily entered an innately aversive chamber to prevent another rat from getting shocked, and c-Fos immunoreactivity in brain regions known to be involved in human empathy-including the anterior cingulate, insula, orbital frontal cortex, and amygdala-correlated with the magnitude of "intersubjective avoidance" each rat displayed. Local field potential recordings revealed that optimal accounts of rats' performance in the task require specific frequencies of LFP oscillations between brain regions in addition to specific frequencies of LFP oscillations within brain regions. Alpha and low gamma coherence between spatially distributed brain regions predicts more intersubjective avoidance, while theta and high gamma coherence between a separate subset of brain regions predicts less intersubjective avoidance. Phase relationship analyses indicated that choice-relevant coherence in the alpha range reflects information passed from the amygdala to cortical structures, while coherence in the theta range reflects information passed in the reverse direction.ConclusionThese results indicate that the frequency-specific "neural context" surrounding brain regions involved in social cognition encodes outcomes of decisions that affect others, above and beyond signals from any set of brain regions in isolation.

Dataset Information

Robust concentration and frequency control in oscillatory homeostats.

Publications

Robust concentration and frequency control in oscillatory homeostats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets