Strength-frequency curve for micromagnetic neurostimulation through EPSPs on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)

Objective: The objective of this study was to measure the effect of micromagnetic stimulation (uMS) on hippocampal neurons, by using single microcoil (ucoil) 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 the ucoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the ucoil 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 the ucoil and its distance over the hippocampal tissue in an in vitro recording setting. Finite element modeling (FEM) of the ucoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V/m). The induced electric field profiles generated at different values of current applied to the ucoil can elicit a neuron response, which was validated by numerical modeling. The modeling settings for the ucoil 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 to uMS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs from uMS while after prolonged TTX washout, a partial recovery of the EPSP from uMS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving the ucoil, 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 for uMS and its unique features related to orientation dependence of the ucoils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related to uMS experiments were studied including ways to overcome them.