Role of Cortical Cell Type and Morphology in Sub- and Suprathreshold Uniform Electric Field Stimulation

By T. Radman, R. Ramos, J. Brumberg, Marom Bikson. Brain Stimulation, 2009

675 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/3e9d005447307990b63854933812749e2ebdef1d

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Citations in the corpus

Direct current stimulation promotes BDNF-dependent synaptic plasticity: Potential implications for motor learning (2010, neutral): “…activation, the estimated shift of the membrane potential ( 0.20 mV in layer V pyramidal neurons, and less in layer II/III pyramidal neurons [Radman et al., 2009]) by electrical field strengths as used in our study (0.75 mV/mm) is more than 50 times lower than the magnitude needed for the…”
A technical guide to tDCS, and related non-invasive brain stimulation tools (2015, neutral): “soma, which may increase excitability (Radman et al., 2009).”
Transcranial alternating current stimulation entrains single-neuron activity in the primate brain (2019, neutral): “Previous work has suggested that tACS might exert two broad classes of influences on neural activity: changes in firing rate (25, 26) and changes in spike timing (27, 28).”
Physiological and modeling evidence for focal transcranial electrical brain stimulation in humans: A basis for high-definition tDCS (2013, methodology): “…target (Rattay, 1986), ongoing activity (Reato et al., 2010), pulse waveform and EF direction (Radman et al., 2009), neuronal activation at 100–200 V/m is broadly consistent with previous animal and modeling studies (Radman et al., 2009; Saypol et al., 1991; Thielscher and Kammer, 2002).”
Optimization of multifocal transcranial current stimulation for weighted cortical pattern targeting from realistic modeling of electric fields (2013, neutral): “) and tangential (E”
The electric field in the cortex during transcranial current stimulation (2013, background): “…distribution of the electric field induced in the grey matter (GM) and white matter (WM), as well as many other factors such as the orientation of the electric field relative to the neurons (Rushton, 1927), cell type and morphology (Radman et al., 2009) or the brain state (Silvanto et al., 2008).”
Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines (2017, background): “These small EFs are considered to be below the intensity required to evoke action potentials in a resting cell (Radman et al., 2009), but likely modify spontaneous firing rates and ongoing processes such as plasticity that are sensitive to polarization levels (Fritsch et al.”
Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: a neurophysiological study. (2013, positive): “Due to the distinctive nature of current direction and EF distribution between the two tDCS configurations applied in the present study, different groups of neurons (for example cortical interneurons or corticospinal neurons) or afferent axons may have been differently modulated depending on their p”
Closing the loop between brain and electrical stimulation: towards precision neuromodulation treatments (2023, background): “…tES induces minor shifts of neural membrane potentials that are too weak to suf ﬁ ciently depolarize cortical neurons to induce action potentials [57], but alter spontaneous brain activity [58, 59]. tES is used in a wide variety of applications in health and disease to change the excitability of…”