CELLULAR MECHANISMS OF EXCITATORY NEURONS DYNAMICS UNDERLYING MAGNETOELECTRIC NANOPARTICLE NEUROMODULATION: A COMPUTATIONAL STUDY

Magnetoelectric Nanoparticles (MENPs) have been proposed as an emerging minimally invasive, wireless neuromodulation approach, promising spatial precision and temporal sensitivity comparable to implanted electrodes. Although their magnetoelectric properties are well characterised, the mechanisms by which MENPs affect neuronal membranes remain poorly understood. Recent experiments in cortical slices expressing slow-wave oscillations provided evidence that MENP stimulation by magnetic fields modulates oscillatory frequency by reducing Down-states (silent periods) duration (Cancino-Fuentes et al., see FENS2026 abstract). Studies in hippocampus cell cultures were unable to conclusively demonstrate that pharmacological blockade of sodium Voltage-gated-Ion Channels (VICs) was sufficient to inhibit MENP-associated spiking activity (Zhang et al. 2022). Accordingly, we hypothesised that MENP stimulation contributes to the modulation of neural firing through increasing the passive ion permeability of the neuronal membrane. To test this hypothesis computationally, we extended the Compte two-compartment (soma - dendrite) pyramidal cell model, capable of slow-wave oscillations, to include MENP-induced leak pores and VICs dependencies. We systematically varied MENP-leak channel dynamics and explored the effects with perturbations of voltage-gated ion channel activation and inactivation. To quantify the impact of these manipulations at the network-level, the single cell model was embedded within a slow-oscillation neuronal network model and state-space analysis was used to assess changes in intrinsic excitability and state stability. Model dynamics were further validated against experimentally recorded local field potential data. This work outlines the individual and combined effects of passive and active membrane properties on neuronal excitability, synthesising plausible cellular-level mechanisms governing MENP neuromodulation, to guide experimental investigation and interpretation.