Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (μ coil)

Abstract

Objective.The objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) prototype, magnetic pen (MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving theµcoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving theμcoil to minimize power will be estimated.Approach.A biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of theμcoil and its distance over the hippocampal tissue in anin vitrorecording setting. Finite element modeling of theμcoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V m^-1). The induced electric field profiles generated at different values of current applied to theµcoil can elicit a neuronal response, which was validated by numerical modeling. The modeling settings for theμcoil were replicated in experiments on rat hippocampal neurons.Main results.The preferred orientation of MagPen over the Schaffer Collateral fibers was demonstrated such that they elicit a neuron response. The recorded EPSPs from CA1 region due toμMS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs fromμMS while after prolonged TTX washout, a partial recovery of the EPSP fromμMS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving theμcoil, led to a decrease in the current amplitude threshold for micromagnetic neurostimulation.Significance.This work reports that micromagnetic neurostimulation can be used to evoke population EPSP responses in the CA1 region of the hippocampus. It demonstrates the strength-frequency curve forµMS and its unique features related to orientation dependence of theµcoils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related toµMS experiments were studied including ways to overcome them.

Keywords: excitatory post synaptic potential (EPSP); hippocampus; microcoil; micromagnetic neurostimulation; spatial selectivity; strength-frequency curve; tetrodotoxin.