Morphology controls how hippocampal CA1 pyramidal neuron responds to uniform electric fields: a biophysical modeling study

Abstract

Responses of different neurons to electric field (EF) are highly variable, which depends on intrinsic properties of cell type. Here we use multi-compartmental biophysical models to investigate how morphologic features affect EF-induced responses in hippocampal CA1 pyramidal neurons. We find that the basic morphologies of neuronal elements, including diameter, length, bend, branch, and axon terminals, are all correlated with somatic depolarization through altering the current sources or sinks created by applied field. Varying them alters the EF threshold for triggering action potentials (APs), and then determines cell sensitivity to suprathreshold field. Introducing excitatory postsynaptic potential increases cell excitability and reduces morphology-dependent EF firing threshold. It is also shown that applying identical subthreshold EF results in distinct polarizations on cell membrane with different realistic morphologies. These findings shed light on the crucial role of morphologies in determining field-induced neural response from the point of view of biophysical models. The predictions are conducive to better understanding the variability in modulatory effects of EF stimulation at the cellular level, which could also aid the interpretations of how applied fields activate central nervous system neurons and affect relevant circuits.