One-dimensional representation of a neuron in a uniform electric field.

The neocortex is the most common target of sub-dural electrotherapy and non-invasive brain stimulation modalities including transcranial magnetic stimulation (TMS) and transcranial direct current simulation (tDCS). Specific neuronal elements targeted by cortical stimulation are considered to underlie therapeutic effects, but the exact cell-type(s) affected by these methods remains poorly understood. We determined if neuronal morphology predicted responses to subthreshold uniform electric fields. We characterized the effects of subthreshold electrical stimulation on identified cortical neurons in vitro. Uniform electric fields were applied to rat motor cortex brain slices, while recording from interneurons and pyramidal cells across cortical layers, using whole cell patch clamp. Neuron morphology was reconstructed following intracellular dialysis of biocytin. Based solely on volume-weighted morphology, we developed a simplified model of neuronal polarization by sub-threshold electric field: an electrotonically linear cylinder that further predicts polarization at distal dendritic tree terminations. We found that neuronal morphology correlated with somatic sub-threshold polarization. Layer V/VI pyramidal neuron somata (individually) and dendrites (averaging across neurons) were most sensitive to sub-threshold fields. This analysis was extended to predict a terminal polarization of a human cortical neuron as 1.44 mV during tDCS.