Mechanism Underlying The Modulation Of Neuronal Spiking With Subthreshold Electric Fields

Transcranial direct current stimulation is a kind of non-invasive brain stimulation technique,which stimulates brain with weak electric fields(EFs).The induced weak subthreshold EFs cannot evoke spiking in individual quiescent neurons.Although transcranial direct current stimulation is widely used in the treatment of neurological diseases and the study of brain function,the underlying mechanism is still unclear.So,the computational neuron model is used to explore the potential mechanism underlying the modulation of neuronal spiking by subthreshold EFs.Firstly,a two-compartment model is adapted to explore how subthreshold EFs influence characteristics of the neuronal spiking.It can be found that the field effects on the spike timing and the spiking rate are maximized at several harmonics of the intrinsic spiking frequency of an active neuron,which implies a potential resonance mechanism.Meanwhile,the neuron morphology and the internal conductance can influence the subthreshold field effects,which can affect the neuronal sensitive to subthreshold EFs.Secondly,the neuronal dynamic threshold is explored with the NEURON simulation platform.It can be found that the neuron morphological property can modulate the spike threshold,and larger membrane area of neurons leads to larger spike threshold,which demonstrates the neuron morphology can affect the neuronal sensitive to subthreshold EFs by modulating spike threshold.Lastly,the simplified neuron model with neuron morphology parameter is built to study the biophysical mechanism of neuron morphology modulating dynamic threshold.By analyzing the competitive relationship of subthreshold ionic currents,it can be discovered that the neuron morphology modulate spike threshold by affecting the somatic internal current.Results above contribute to uncovering the relevant mechanism of subthreshold EFs effects on neuron spiking,which has important theoretical significance in reasonably designing the transcranial direct current stimulation strategy,optimizing the stimulation plan and improving the stimulation device.