Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro

Abstract

Background The neocortex is the most common target of sub-dural electrotherapy and non-invasive brain stimulation modalities including transcranial magnetic stimulation (TMS) and transcranial current simulation (TCS). 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. Objective We determined if neuronal morphology or cell type predicted responses to sub- and suprathreshold uniform electric fields. Methods We characterized the effects of sub- and supra-threshold 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 parsimonious model of neuronal soma polarization by sub-threshold electric fields. Results We found that neuronal morphology correlated with somatic sub-threshold polarization. Based on neuronal morphology, we predict layer V pyramidal neuronal soma to be the most sensitive to polarization by optimally oriented sub-threshold fields. Supra-threshold electric field action potential threshold was shown to reflect both direct cell polarization and synaptic (network) activation. Layer V/VI neuron absolute electric field action potential thresholds were lower than Layer II/III pyramidal neurons and interneurons. Compared to somatic current injection, electric fields promoted burst firing and modulated action potential firing times.