Training deep neural density estimators to identify mechanistic models of neural dynamics

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Sept. 17, 2020

Mechanistic modeling in neuroscience aims to explain observed phenomena terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge machine learning tool uses deep density estimators—trained using simulations—to carry out Bayesian inference retrieve the full space compatible raw or selected features. Our method is scalable features can rapidly analyze new after initial training. demonstrate power flexibility our approach on receptive fields, ion channels, Hodgkin–Huxley models. also characterize circuit configurations giving rise rhythmic activity crustacean stomatogastric ganglion, use these results derive hypotheses for compensation mechanisms. will help close gap between data-driven theory-driven models dynamics.

Language: Английский

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Ion Channel Degeneracy, Variability, and Covariation in Neuron and Circuit Resilience

Annual Review of Neuroscience, Journal Year: 2021, Volume and Issue: 44(1), P. 335 - 357

Published: March 26, 2021

The large number of ion channels found in all nervous systems poses fundamental questions concerning how the characteristic intrinsic properties single neurons are determined by specific subsets they express. All display many different with overlapping voltage- and time-dependent properties. We speculate that these promote resilience neuronal function. Individual same cell type show variability channel conductance densities even though can generate reliable similar behavior. This complicates a simple assignment function to any is associated variable responses perturbations, deletions, pharmacological manipulation. Ion genes often strong positively correlated expression, which may result from molecular developmental rules determine expressed given type.

Language: Английский

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A taxonomy of seizure dynamotypes

eLife, Journal Year: 2020, Volume and Issue: 9

Published: July 21, 2020

Seizures are a disruption of normal brain activity present across vast range species and conditions. We introduce an organizing principle that leads to the first objective Taxonomy Seizure Dynamics (TSD) based on bifurcation theory. The 'dynamotype' seizure is dynamic composition defines its observable characteristics, including how it starts, evolves ends. Analyzing over 2000 focal-onset seizures from multiple centers, we find evidence all 16 dynamotypes predicted in TSD. demonstrate patients' evolve during their lifetime display complex but systematic variations hierarchy (certain types more common), non-bijectivity (a patient may types) pairing preference (multiple occur one seizure). TSD provides way stratify patients complement clinical classifications, language describe most critical features dynamics, framework guide future research focused dynamical properties.

Language: Английский

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Degeneracy in epilepsy: multiple routes to hyperexcitable brain circuits and their repair

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: May 3, 2023

Abstract Due to its complex and multifaceted nature, developing effective treatments for epilepsy is still a major challenge. To deal with this complexity we introduce the concept of degeneracy field research: ability disparate elements cause an analogous function or malfunction. Here, review examples epilepsy-related at multiple levels brain organisation, ranging from cellular network systems level. Based on these insights, outline new multiscale population modelling approaches disentangle web interactions underlying design personalised multitarget therapies.

Language: Английский

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A biophysical perspective on the resilience of neuronal excitability across timescales

Nature reviews. Neuroscience, Journal Year: 2023, Volume and Issue: 24(10), P. 640 - 652

Published: Aug. 24, 2023

Language: Английский

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Comprehensive machine learning analysis of Hydra behavior reveals a stable basal behavioral repertoire

eLife, Journal Year: 2018, Volume and Issue: 7

Published: March 28, 2018

Animal behavior has been studied for centuries, but few efficient methods are available to automatically identify and classify it. Quantitative behavioral studies have hindered by the subjective imprecise nature of human observation, slow speed annotating data. Here, we developed an automatic analysis pipeline cnidarian Hydra vulgaris using machine learning. We imaged freely behaving Hydra, extracted motion shape features from videos, constructed a dictionary visual pre-defined behaviors. also identified unannotated behaviors with unsupervised methods. Using this pipeline, quantified 6 basic found surprisingly similar statistics across animals within same species, regardless experimental conditions. Our indicates that fundamental repertoire is stable. This robustness could reflect homeostatic neural control "housekeeping" which already present in earliest nervous systems.

Language: Английский

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Temperature compensation in a small rhythmic circuit

eLife, Journal Year: 2020, Volume and Issue: 9

Published: June 2, 2020

Temperature affects the conductances and kinetics of ionic channels that underlie neuronal activity. Each membrane conductance has a different characteristic temperature sensitivity, which raises question how neurons circuits can operate robustly over wide ranges. To address this, we employed computational models pyloric network crabs lobsters. We produced multiple exhibit triphasic rhythm range temperatures explored dynamics their currents they change with temperature. produce smooth changes in relative contributions to neural activity so networks undergo graceful transitions mechanisms give rise patterns. Moreover, responses deletions current be at high low temperatures, indicating even well-defined genetic or pharmacological manipulation may qualitatively distinct effects depending on

Language: Английский

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The structure of behavioral variation within a genotype

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Oct. 19, 2021

Individual animals vary in their behaviors. This is true even when they share the same genotype and were reared environment. Clusters of covarying behaviors constitute behavioral syndromes, an individual's position along such axes covariation a representation personality. Despite these conceptual frameworks, structure within essentially uncharacterized its mechanistic origins unknown. Passing hundreds inbred Drosophila individuals through experimental pipeline that captured measures, we found sparse but significant correlations among small sets Thus, space variation has many independent dimensions. Manipulating physiology brain, specific neural populations, altered correlations. We also observed gene expression can predict on some axes. work represents first steps understanding biological mechanisms determining genotype.

Language: Английский

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Multiscale Computer Model of the Spinal Dorsal Horn Reveals Changes in Network Processing Associated with Chronic Pain

Journal of Neuroscience, Journal Year: 2022, Volume and Issue: 42(15), P. 3133 - 3149

Published: March 1, 2022

Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to brain. That processing profoundly influences whether stimuli are correctly or incorrectly perceived as painful. Significant advances have been made identifying types of excitatory and inhibitory neurons that comprise SDH, there some information about how neuron connected, but it remains unclear overall circuit processes disrupted under chronic pain conditions. To explore SDH function, we developed a computational model tightly constrained by experimental data. Our comprises conductance-based models reproduce characteristic firing patterns neurons. Excitatory populations, defined their expression genetic markers, spiking pattern, morphology, were synaptically connected according available qualitative Using algorithm, synaptic weights tuned projection rates (model output) based on primary afferent input) across range mechanical stimulus intensities. Disparate weight combinations could produce equivalent revealing degeneracy may underlie heterogeneous responses different circuits perturbations pathologic insults. validate our model, verified responded reduction inhibition (i.e., disinhibition) ablation specific manner consistent with experiments. Thus validated, offers valuable resource for interpreting results testing hypotheses

Language: Английский

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New insights from small rhythmic circuits

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 76, P. 102610 - 102610

Published: Aug. 17, 2022

Small rhythmic circuits, such as those found in invertebrates, have provided fundamental insights into how circuit dynamics depend on individual neuronal and synaptic properties. Degenerate circuits are with different network parameters similar behavior. New work degenerate their modulation illustrates some of the rules that help maintain stable robust function despite environmental perturbations. Advances neuropeptide isolation identification provide enhanced understanding neuromodulation for The advent molecular studies mRNA expression provides new insight animal-to-animal variability homeostatic regulation excitability neurons networks.

Language: Английский

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