Simulation Study On Electrical Stimulation Of Entorhinal Cortex In Mice

There is no effective cure for Alzheimer’s disease(AD)at this stage.Deep brain stimulation(DBS)is a research hotspot in AD treatment,which implants stimulation electrodes in specific structures of brain and generate external electric fields to regulate pathological neural activity.Entorhinal cortex(EC)is the earliest damaged structure in AD,so it is one of the most valuable stimulation targets.The therapeutic mechanism of electrical stimulation in entorhinal cortex needs to be studied through animal experiments,but the influence of different stimulation parameters on the therapeutic effect is rarely considered in the research process.In order to optimize the choice of stimulus parameters in animal experiments,this study established a finite element electric field model simulating electrically stimulated entorhinal cortex of mice and an entorhinal cortical neuron model to study the response of neurons to the electric field under different stimulation conditions.The detailed research work includes three aspects.Firstly,use COMSOL Multiphysics finite element software to model and simulate the electric field distribution generated by the current stimulation in the entorhinal cortex of mice.Then,use NEURON software to establish a neuron model for pyramidal neurons in the entorhinal cortex that was highly excitable in the entorhinal cortex,the electric field simulation result was set as the input of its extracellular stimulation.Finally,use models to study the influence of stimulation parameters and electrode-neuron relative position on the excitability threshold of resting neurons,and analyze the influence of different stimulation parameters on the response frequency of firing neurons.The simulation results show: increasing the stimulation pulse width can reduce the activation threshold of resting pyramidal neurons;Taking into account electrical safety,the stimulation pulse width in the range of 60-100 μs is more efficient;For the firing neuron,electrical stimulation below the activation threshold can still change its firing frequency.the response threshold of neurons mainly depends on the stimulation intensity and pulse width,and the response frequency is more affected by the stimulation frequency.For the bipolar concentric stimulation electrode used in this study,high stimulation intensity may activate neurons in deep cortical layer with somas away from the cathode and axons close to the anode.The results of this simulation study provide some guidance for rational selection of stimulation parameters and improvement of stimulation targeting in EC-DBS experiments of mouse.