Adam J. H. Newton

Multiscale models of neurons, tissue and disease

Computational neuroscience

I build biophysically detailed, multiscale models of neural tissue, from ion channels, pumps and diffusion to cellular metabolism, to understand why some neurons and circuits are vulnerable to disease while others are resilient.

Most of my work is on spreading depolarization, the slow wave of near-complete depolarization that accompanies ischemic stroke, migraine aura and brain injury, and on cell-to-cell variability in primary motor cortex. I am a developer of the NEURON simulator, where I helped build the reaction-diffusion module that lets electrophysiology models include the ion and metabolite dynamics they usually leave out.

Research highlights

Pyramidal neuron colored by intracellular calcium, highest in the basal dendrites

Vulnerable dendrites

Ischemia and spreading depolarization load different parts of the dendritic tree with calcium and chloride.

 Schematic of a model neuron with pumps, cotransporters and channels in the extracellular space

Tissue-scale SD

Tens of thousands of neurons, ions and oxygen in the extracellular space of a slice and of cortex.

 Simulated potassium spreading through extracellular space around a population of cells

NEURON reaction-diffusion

Simulation tools for ions and molecules inside cells and in the extracellular space.

Recent publications

  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. 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
  3. 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

All publications →