Modernizing the NEURON Simulator for Sustainability, Portability, and Performance

Frontiers in Neuroinformatics, Journal Year: 2022, Volume and Issue: 16

Published: June 27, 2022

The need for reproducible, credible, multiscale biological modeling has led to the development of standardized simulation platforms, such as widely-used NEURON environment computational neuroscience. Developing and maintaining over several decades required attention competing needs backwards compatibility, evolving computer architectures, addition new scales physical processes, accessibility users, efficiency flexibility specialists. In order meet these challenges, we have now substantially modernized NEURON, providing continuous integration, an improved build system release workflow, better documentation. With help a source-to-source compiler NMODL domain-specific language enhanced NEURON's ability run efficiently, via CoreNEURON engine, on variety hardware including GPUs. Through implementation optimized in-memory transfer mechanism this performance backend is made easily accessible training model-development paths from laptop workstation supercomputer cloud platform. Similarly, been able accelerate reaction-diffusion through use just-in-time compilation. We show that efforts growing developer base, simpler more robust software distribution, wider range supported integration with other scientific workflows, biophysical biochemical models.

Language: Английский

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Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

Cell Reports, Journal Year: 2023, Volume and Issue: 42(11), P. 113378 - 113378

Published: Nov. 1, 2023

We developed a detailed model of macaque auditory thalamocortical circuits, including primary cortex (A1), medial geniculate body (MGB), and thalamic reticular nucleus, utilizing the NEURON simulator NetPyNE tool. The A1 simulates cortical column with over 12,000 neurons 25 million synapses, incorporating data on cell-type-specific neuron densities, morphology, connectivity across six layers. It is reciprocally connected to MGB thalamus, which includes interneurons core matrix-layer-specific projections A1. multiscale measures, physiological firing rates, local field potentials (LFPs), current source densities (CSDs), electroencephalography (EEG) signals. Laminar CSD patterns, during spontaneous activity in response broadband noise stimulus trains, mirror experimental findings. Physiological oscillations emerge spontaneously frequency bands comparable those recorded vivo. elucidate population-specific contributions observed oscillation events relate them presynaptic input patterns. offers quantitative theoretical framework integrate interpret predict its underlying cellular circuit mechanisms.

Language: Английский

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Data-driven multiscale computational models of cortical and subcortical regions

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 85, P. 102842 - 102842

Published: Feb. 5, 2024

Language: Английский

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Methods and considerations for estimating parameters in biophysically detailed neural models with simulation based inference

PLoS Computational Biology, Journal Year: 2024, Volume and Issue: 20(2), P. e1011108 - e1011108

Published: Feb. 26, 2024

Biophysically detailed neural models are a powerful technique to study dynamics in health and disease with growing number of established openly available models. A major challenge the use such is that parameter inference an inherently difficult unsolved problem. Identifying unique distributions can account for observed dynamics, differences across experimental conditions, essential their meaningful use. Recently, simulation based (SBI) has been proposed as approach perform Bayesian estimate parameters SBI overcomes not having access likelihood function, which severely limited methods models, by leveraging advances deep learning density estimation. While substantial methodological advancements offered promising, large scale biophysically challenging doing so have established, particularly when inferring time series waveforms. We provide guidelines considerations on how be applied waveforms starting simplified example extending specific applications common MEG/EEG using modeling framework Human Neocortical Neurosolver. Specifically, we describe compare results from oscillatory event related potential simulations. also diagnostics used assess quality uniqueness posterior estimates. The described principled foundation guide future wide variety dynamics.

Language: Английский

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Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: May 17, 2023

Summary Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which are challenging to study in vivo . Large-scale, biophysically detailed models offer a tool can complement laboratory approaches. We present model comprising eight somatosensory cortex subregions, 4.2 million morphological electrically-detailed neurons, 13.2 billion local mid-range synapses. In silico tools enabled reproduction extension of experiments under single parameterization, providing strong validation. The reproduced millisecond-precise stimulus-responses, stimulus-encoding targeted optogenetic activation, selective propagation stimulus-evoked activity downstream areas. model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, cortical is shaped by high-dimensional connectivity motifs connectivity, spatial targeting rules inhibitory subpopulations. latter was facilitated using rewired connectome included specific observed different neuron types electron microscopy. also predicted the role interneuron layers stimulus encoding. Simulation large subvolume made available enable further community-driven improvement, validation investigation.

Language: Английский

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Large-scale biophysically detailed model of somatosensory thalamocortical circuits in NetPyNE

Frontiers in Neuroinformatics, Journal Year: 2022, Volume and Issue: 16

Published: Sept. 22, 2022

The primary somatosensory cortex (S1) of mammals is critically important in the perception touch and related sensorimotor behaviors. In 2015, Blue Brain Project (BBP) developed a groundbreaking rat S1 microcircuit simulation with over 31,000 neurons 207 morpho-electrical neuron types, 37 million synapses, incorporating anatomical physiological information from wide range experimental studies. We have implemented this highly detailed complex model NetPyNE, using data available Neocortical Microcircuit Collaboration Portal. NetPyNE provides Python high-level interface to NEURON allows defining complicated multiscale models an intuitive declarative standardized language. It also facilitates running parallel simulations, automates optimization exploration parameters supercomputers, built-in analysis functions. This will make more accessible simpler scale, modify extend order explore research questions or interconnect other existing models. Despite some implementation differences, preserved original cell morphologies, electrophysiological responses spatial distribution for all types; connectivity properties 1941 pathways, including synaptic dynamics short-term plasticity (STP). simulations produced reasonable firing rates activity patterns across populations. When STP was included, network generated 1 Hz oscillation comparable vitro -like state. By then reducing extracellular calcium concentration, reproduced vivo states asynchronous activity. These results validate study new modeling tool. Simulated local field potentials (LFPs) exhibited realistic oscillatory features, distance- frequency-dependent attenuation. extended by adding thalamic circuits, 6 distinct populations intrathalamic, thalamocortical (TC) corticothalamic derived data. single known circuit-level dynamics, burst tonic modes patterns, providing input enabling TC interactions. Overall, our work widely accessible, data-driven biophysically-detailed circuits that can be employed as community tool researchers neural function disease.

Language: Английский

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Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part II: Physiology and Experimentation

Published: Nov. 8, 2024

Cortical dynamics underlie many cognitive processes and emerge from complex multi-scale interactions, which are challenging to study in vivo . Large-scale, biophysically detailed models offer a tool can complement laboratory approaches. We present model comprising eight somatosensory cortex subregions, 4.2 million morphological electrically-detailed neurons, 13.2 billion local mid-range synapses. In silico tools enabled reproduction extension of experiments under single parameterization, providing strong validation. The reproduced millisecond-precise stimulus-responses, stimulus-encoding targeted optogenetic activation, selective propagation stimulus-evoked activity downstream areas. model’s direct correspondence with biology generated predictions about how multiscale organization shapes activity; for example, cortical is shaped by high-dimensional connectivity motifs connectivity, spatial targeting rules inhibitory subpopulations. latter was facilitated using rewired connectome included specific observed different neuron types electron microscopy. also predicted the role interneuron layers stimulus encoding. Simulation large subvolume made available enable further community-driven improvement, validation investigation.

Language: Английский

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Decreased cellular excitability of pyramidal tract neurons in primary motor cortex leads to paradoxically increased network activity in simulated parkinsonian motor cortex

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 11, 2025

Recent evidence suggests that the primary motor cortex (M1) layer 5B pyramidal tract (PT5B) neurons show a decreased intrinsic excitability in mouse models of parkinsonism, which perhaps plays an important role pathophysiology parkinsonian symptoms. PT5B project to outputs brainstem and spinal cord, leading direct expression Parkinson’s disease (PD) pathology. We set out explore how neuron influences activity patterns M1 network. Using NEURON/NetPyNE simulators, we implemented detailed computer simulations based on control 6-OHDA-treated slice data. placed these cells in vivo network simulation, driven by ascending input from thalamus other cortical areas. Simulated otherwise unmodified simulated resulted major changes LFP oscillatory power condition: order magnitude increase beta band around 15 Hz rest state lesser activated (movement) state. demonstrated relatively small altered throughout circuit. In particular, increased power, is signature PD pathophysiology.

Language: Английский

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A multiscale electro-metabolic model of a rat neocortical circuit reveals the impact of ageing on central cortical layers

PLoS Computational Biology, Journal Year: 2025, Volume and Issue: 21(5), P. e1013070 - e1013070

Published: May 20, 2025

The high energetic demands of the brain arise primarily from neuronal activity. Neurons consume substantial energy to transmit information as electrical signals and maintain their resting membrane potential. These requirements are met by neuro-glial-vascular (NGV) ensemble, which generates in a coupled metabolic process. In ageing, function becomes impaired, producing less and, consequently, system is unable sustain needs. We propose multiscale model electro-metabolic coupling reconstructed rat neocortex. This combines an electro-morphologically electrophysiological with detailed NGV model. Our results demonstrate that large-scale effectively captures processes at circuit level, highlighting importance heterogeneity within circuit, where vary according characteristics. Finally, our indicates middle cortical layers particularly vulnerable impairment.

Language: Английский

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Decreased cellular excitability of pyramidal tract neurons in primary motor cortex leads to paradoxically increased network activity in simulated parkinsonian motor cortex

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

Published: May 23, 2024

Abstract Decreased excitability of pyramidal tract neurons in layer 5B (PT5B) primary motor cortex (M1) has recently been shown a dopamine-depleted mouse model parkinsonism. We hypothesized that decreased PT5B neuron would substantially disrupt oscillatory and non-oscillatory firing patterns 5 (L5) (M1). To test this hypothesis, we performed computer simulations using previously validated M1. Inclusion the experimentally identified parkinsonism-associated decrease into our computational produced paradoxical increase rest-state rate, as well an beta-band power local field potential (LFP). In movement-state, population LFP showed reduced beta increased high-beta, low-gamma activity 20-35 Hz parkinsonian, but not control condition. The appearance oscillations parkinsonism be expected to normal M1 output contribute deficits seen patients with Parkinson’s disease (PD).

Language: Английский

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