Myelin Governs Hippocampal Network Function through the Extracellular Space it Occupies, Not Only the Axons it Insulates

Demyelination in hippocampal CA1 enlarges the extracellular space (volume fraction 28% to 43%, up to 70% across layers) and shifts network activity, including transmission failure below four of sixteen myelin wraps.

• Why it matters: Myelin both insulates axons and occupies extracellular volume, but how these roles jointly affect neurotransmitter diffusion, clearance, and circuit dynamics is unclear.
• What they did: A multiscale model coupled lattice Boltzmann simulations of ECS flow with reconstructed CA1 neuron–glia networks; demyelination changed ECS tortuosity (~1.7 to 1.4) and effective diffusivity (0.35 to 0.50), and wrap-dependent synaptic outcomes were tested in 200-cell networks.
• The result: Demyelination shortened breakthrough times by roughly a third, halved firing (7.9 to 4.4 Hz), reduced band power up to 8.7-fold, and displaced population state (100% classifier accuracy), while continuous myelin modulation (to 12.5% and back) restored baseline thresholds, firing, and spectral power.

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