Modernizing the NEURON Simulator for Sustainability, Portability, and Performance

Frontiers in Neuroinformatics, Год журнала: 2022, Номер 16

Опубликована: Июнь 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.

Язык: Английский

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Multiscale model of primary motor cortex circuits predicts in vivo cell-type-specific, behavioral state-dependent dynamics

Cell Reports, Год журнала: 2023, Номер 42(6), С. 112574 - 112574

Опубликована: Июнь 1, 2023

Understanding cortical function requires studying multiple scales: molecular, cellular, circuit, and behavioral. We develop a multiscale, biophysically detailed model of mouse primary motor cortex (M1) with over 10,000 neurons 30 million synapses. Neuron types, densities, spatial distributions, morphologies, biophysics, connectivity, dendritic synapse locations are constrained by experimental data. The includes long-range inputs from seven thalamic regions noradrenergic inputs. Connectivity depends on cell class depth at sublaminar resolution. accurately predicts in vivo layer- cell-type-specific responses (firing rates LFP) associated behavioral states (quiet wakefulness movement) manipulations (noradrenaline receptor blockade thalamus inactivation). generate mechanistic hypotheses underlying the observed activity analyzed low-dimensional population latent dynamics. This quantitative theoretical framework can be used to integrate interpret M1 data sheds light multiscale dynamics several conditions behaviors.

Язык: Английский

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

PLoS Computational Biology, Год журнала: 2024, Номер 20(2), С. e1011108 - e1011108

Опубликована: Фев. 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.

Язык: Английский

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Detecting Spontaneous Neural Oscillation Events in Primate Auditory Cortex

eNeuro, Год журнала: 2022, Номер 9(4), С. ENEURO.0281 - 21.2022

Опубликована: Июль 1, 2022

Electrophysiological oscillations in the brain have been shown to occur as multicycle events, with onset and offset dependent on behavioral cognitive state. To provide a baseline for state-related task-related we quantified oscillation features resting-state recordings. We developed an open-source wavelet-based tool detect characterize such events (OEvents) exemplify use of this both simulations two invasively-recorded electrophysiology datasets: one from human, nonhuman primate (NHP) auditory system. After removing incidentally occurring event-related potentials (ERPs), used OEvents quantify features. identified ∼2 million classified within traditional frequency bands: δ, θ, α, β, low γ, high γ. Oscillation 1-44 cycles could be at least band 90% time human NHP Individual were characterized by nonconstant amplitude. This result necessarily contrasts prior studies which assumed constancy, but is consistent evidence event-associated oscillations. measured event duration, span, waveform shape. Oscillations tended exhibit multiple per event, verifiable comparing filtered unfiltered waveforms. In addition clear intraevent rhythmicity, there was also interevent rhythmicity bands, demonstrated finding that coefficient variation interval distributions Fano factor (FF) measures differed significantly Poisson distribution assumption. Overall, our study provides easy-to-use single-trial level or ongoing recordings, demonstrates rhythmic, dominate cortical dynamics.

Язык: Английский

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A connectome manipulation framework for the systematic and reproducible study of structure function relationships through simulations

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 26, 2024

ABSTRACT Synaptic connectivity at the neuronal level is characterized by highly non-random features. Hypotheses about their role can be developed correlating structural metrics to functional But prove causation, manipula- tions of would have studied. However, fine-grained scale which trends are expressed makes this approach challenging pursue experimentally. Simulations networks provide an alternative route study arbitrarily complex manipulations in morphologically and biophysically detailed models. Here, we present Connectome-Manipulator, a Python framework for rapid connectome large- network models SONATA format. In addition creating or manipulating model, it provides tools fit parameters stochastic against existing connectomes. This enables replacement any with equivalent connectomes different levels complexity, transplantation features from one another, systematic study. We employed model rat somatosensory cortex two exemplary use cases: transplanting interneuron electron microscopy data simplified excitatory connectivity. ran series simulations found diverse shifts activity individual neuron populations causally linked these manipulations.

Язык: Английский

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A ubiquitous spectrolaminar motif of local field potential power across the primate cortex?

Опубликована: Апрель 11, 2024

This is a commentary on recently published paper. Mendoza-Halliday, Major et al., 2024 (“The Paper”) advocates local field potential (LFP)-based approach to functional identification of cortical layers during “laminar” multielectrode recordings in nonhuman primates (NHPs). The broader goal substantiate the hypothesis ubiquitous spectrolaminar motif NHP neocortex: gamma range activity originates upper and reflects feedforward activity, while alpha-beta lower feedback activity. In an impressive scientific effort, authors analyze data (simultaneous from all layers) collected 14 areas 2 prior macaque studies compare them marmoset, mouse, human data. Despite Paper’s strengths, its for impact, series concerns that are fundamental analysis interpretation signals, question foundations. Paper also overstates strength prevalence it advocates, understates key strengths nuances work.

Язык: Английский

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Spike frequency adaptation in primate lateral prefrontal cortex neurons results from interplay between intrinsic properties and circuit dynamics

Cell Reports, Год журнала: 2025, Номер 44(1), С. 115159 - 115159

Опубликована: Янв. 1, 2025

Язык: Английский

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NeoCoMM: Neocortical neuro-inspired computational model for realistic microscale simulations

SoftwareX, Год журнала: 2025, Номер 30, С. 102108 - 102108

Опубликована: Март 3, 2025

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Laminar specificity of the auditory perceptual awareness negativity: A biophysical modeling study

PLoS Computational Biology, Год журнала: 2023, Номер 19(6), С. e1011003 - e1011003

Опубликована: Июнь 29, 2023

How perception of sensory stimuli emerges from brain activity is a fundamental question neuroscience. To date, two disparate lines research have examined this question. On one hand, human neuroimaging studies helped us understand the large-scale dynamics perception. other work in animal models (mice, typically) has led to insight into micro-scale neural circuits underlying However, translating such humans been challenging. Here, using biophysical modeling, we show that auditory awareness negativity (AAN), an evoked response associated with target sounds noise, can be accounted for by synaptic input supragranular layers cortex (AC) present when are heard but absent they missed. This additional likely arises cortico-cortical feedback and/or non-lemniscal thalamic projections and targets apical dendrites layer-5 (L5) pyramidal neurons. In turn, leads increased local field potential activity, spiking L5 neurons, AAN. The results consistent current cellular conscious processing help bridge gap between macro micro levels perception-related activity.

Язык: Английский

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In-silico testing of new pharmacology for restoring inhibition and human cortical function in depression

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Фев. 23, 2024

Abstract Reduced inhibition by somatostatin-expressing interneurons is associated with depression. Administration of positive allosteric modulators α5 subunit-containing GABA A receptor (α5-PAM) that selectively target this lost exhibit antidepressant and pro-cognitive effects in rodent models chronic stress. However, the functional α5-PAM on human brain vivo are unknown, currently cannot be assessed experimentally. We modeled tonic as measured neurons, tested silico detailed cortical microcircuits health found effectively recovered impaired processing quantified stimulus detection metrics, also power spectral density profile microcircuit EEG signals. performed an dose-response identified simulated biomarker candidates. Our results serve to de-risk facilitate translation provide biomarkers non-invasive signals for monitoring engagement drug efficacy.

Язык: Английский

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