Adam J. H. Newton

Multiscale models of neurons, tissue and disease

Publications

Each entry links to the paper and, where one exists, to the model code on ModelDB. Also on Google Scholar and ORCID.

Journal articles

  1. Computer models predict differential dendritic vulnerability with ischemia and spreading depression Newton AJH, Lytton WW, DiStasio M, McDougal RA 2026PLOS Computational Biology 22, e1014701

    In a morphologically detailed model of a hippocampal CA1 pyramidal neuron, calcium accumulates most in the basal dendrites during both ischemia and spreading depolarization, suggesting they are most exposed to excitotoxicity. Only ischemia exposes the distal apical dendrites to high chloride, a possible route to dendritic beading.

    PaperModel on ModelDB
  2. Capillary Density and Neuronal Homeostasis in Human Primary Visual Cortex Wang Y, Guo A, Newton AJH, McDougal RA, Lytton WW, DiStasio MM 2026Microcirculation 33, e70064

    Measures the distance between more than 155,000 neurons and 84,000 vascular profiles across the layers of human primary visual cortex. Neurons in the middle layers sit closest to capillaries. These measurements set where capillaries sit in our cortical models of spreading depolarization.

    Paper
  3. Biophysical modelling of intrinsic cardiac nervous system neuronal electrophysiology based on single‐cell transcriptomics Gupta S, Gee MM, Newton AJH, Kuttippurathu L, Moss A, Tompkins JD, Schwaber JS, Vadigepalli R, Lytton WW 2025Journal of Physiology 603, 2119–2138

    A library of electrophysiological models of neurons in the heart's intrinsic cardiac nervous system, each built from the ion channels found in single-cell transcriptomic data. Like the real neurons, most models fire phasically.

    Paper
  4. Downmodulation of Potassium Conductances Induces Epileptic Seizures in Cortical Network Models Via Multiple Synergistic Factors Ho ECY, Newton AJH, Urdapilleta E, Dura-Bernal S, Truccolo W 2025Journal of Neuroscience 45, e1909232025

    Cortical network models with potassium diffusion and glial buffering show how reducing voltage-gated K+ conductance, as 4-aminopyridine does, broadens action potentials, drives fast-spiking interneurons into depolarization block and produces seizure-like synchrony.

    PaperModel on ModelDB
  5. Unpacking the multimodal, multi‐scale data of the fast and slow lanes of the cardiac vagus through computational modelling Gee MM, Hornung E, Gupta S, Newton AJH, Cheng Z, Lytton WW, Lenhoff AM, Schwaber JS, Vadigepalli R 2024Experimental Physiology 109, 1994–2000

    A review setting out how computational models can integrate molecular, cellular and physiological data on the fast and slow vagal pathways that regulate the heart.

    Paper
  6. A pipeline for the retrieval and extraction of domain-specific information with application to COVID-19 immune signatures Newton AJH, Chartash D, Kleinstein SH, McDougal RA 2023BMC Bioinformatics 24, 292

    A classifier built on document embeddings, trained iteratively with expert review, finds papers reporting human COVID-19 immune signatures with an 86% positive predictive value; a semi-automated system then asks the authors for the signatures.

    Paper
  7. Multiscale Computer Modeling of Spreading Depolarization in Brain Slices Kelley C, Newton AJH, Hrabetova S, McDougal RA, Lytton WW 2022eNeuro 9, ENEURO.0082-22.2022

    A model of 36,000 neurons in the extracellular space of a brain slice, with K+, Na+, Cl− and O2 diffusion, reproduces spreading depolarization at realistic speeds and predicts that extracellular volume, neuronal density and oxygenation control its spread.

    PaperModel on ModelDB
  8. Conditions for Synaptic Specificity during the Maintenance Phase of Synaptic Plasticity Huertas MA, Newton AJH, McDougal RA, Sacktor TC, Shouval HZ 2022eNeuro 9, ENEURO.0064-22.2022

    Analysis and reaction-diffusion simulations in NEURON show that synapse-specific maintenance of plasticity requires the molecular switch, such as PKMζ, to reside in dendritic spines, which sets strict limits on protein diffusion, turnover and spine shape.

    PaperModel on ModelDB
  9. Modernizing the NEURON Simulator for Sustainability, Portability, and Performance Awile O, Kumbhar P, Cornu N, Dura-Bernal S, King JG, Lupton O, Magkanaris I, McDougal RA, Newton AJH, Pereira F, Săvulescu A, Carnevale NT, Lytton WW, Hines ML, Schürmann F 2022Frontiers in Neuroinformatics 16, 884046

    How NEURON was modernized: continuous integration, a new build and release workflow, GPU support through CoreNEURON and the NMODL compiler, and Just-In-Time compilation that speeds up reaction-diffusion simulations.

    Paper
  10. Efficient Simulation of 3D Reaction-Diffusion in Models of Neurons and Networks McDougal RA, Conte C, Eggleston L, Newton AJH, Galijasevic H 2022Frontiers in Neuroinformatics 16, 847108

    A finite-volume method in NEURON for 3D intracellular reaction-diffusion, coupled to NEURON's 1D electrophysiology. It captures dynamics in spines and near the soma that 1D simulations miss.

    PaperModel on ModelDB
  11. Neuron Names: A Gene- and Property-Based Name Format, With Special Reference to Cortical Neurons Shepherd GM, Marenco L, Hines ML, Migliore M, McDougal RA, Carnevale NT, Newton AJH, Surles-Zeigler M, Ascoli GA 2019Frontiers in Neuroanatomy 13, 25

    A naming format for neuron types that carries gene expression and functional properties alongside anatomical location, with examples from mouse cortex.

    Paper
  12. Using NEURON for Reaction-Diffusion Modeling of Extracellular Dynamics Newton AJH, McDougal RA, Hines ML, Lytton WW 2018Frontiers in Neuroinformatics 12, 41

    Introduces extracellular reaction-diffusion in NEURON. Tissue is described by its free volume fraction and tortuosity, so models can include regional differences and pathology; illustrated with spreading depression.

    PaperModel on ModelDB
  13. Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations Newton AJH, Wall MJ, Richardson MJE 2017Journal of Neurophysiology 117, 937–949

    Modeling and experiments show that microelectrode biosensors calibrated in free flow underestimate concentrations in tissue: the sensor consumes the analyte it measures, creating a depletion gradient that tissue porosity and tortuosity make worse.

    Paper
  14. Computer modeling of ischemic stroke Newton AJH, Lytton WW 2016Drug Discovery Today: Disease Models 19, 77–83

    A review of multiscale computer modeling of ischemic stroke, from molecules to tissue, as a route to multi-target neuroprotective therapies.

    Paper

Book chapters

  1. Brain Ischemia and Stroke Newton AJH, Seidenstein A, Neymotin SA, Taxin Z, Mohan A, Lipton P 2022In: Jaeger D, Jung R (eds), Encyclopedia of Computational Neuroscience. Springer, pp. 562–569

    Encyclopedia entry on modeling cerebral ischemia, from the loss of oxygen and glucose supply to the many pathways of cell death across spatial and temporal scales.

    Paper
  2. Modeling of Disease: Physical and Molecular Level, Overview Newton AJH, Lytton WW 2022In: Jaeger D, Jung R (eds), Encyclopedia of Computational Neuroscience. Springer, pp. 77–81

    Overview of the encyclopedia section on physical- and molecular-scale models of disease and their place in translating basic research to the clinic.

    Paper
  3. Computational Neuroscience of Neuronal Networks Newton AJH, Neymotin SA, Mathew A, Kerr CC, Lytton WW 2022In: Pfaff DW, Volkow ND, Rubenstein JL (eds), Neuroscience in the 21st Century. Springer, pp. 3421–3459

    An introduction to modeling networks of tens to millions of neurons, and to deciding what to simplify when crossing spatial and temporal scales.

    Paper
  4. Computational Neuroscience of Synapses and Neurons Newton AJH, Neymotin SA, Kerr CC, Lytton WW 2022In: Pfaff DW, Volkow ND, Rubenstein JL (eds), Neuroscience in the 21st Century. Springer, pp. 3381–3410

    An introduction to simulating neurons and synapses, from the membrane as a capacitor and resistor to multicompartment models.

    Paper

Thesis

  1. Modelling adenosine dynamics in neural tissues Newton AJH 2015PhD thesis, University of Warwick

    A macroscopic model of adenosine clearance in neural tissue, built from the literature and validated against experiments.