title: Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects.
abstract: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique to modulate cortical excitability. Although increased/decreased excitability under the anode/cathode electrode is nominally associated with membrane depolarization/hyperpolarization, which cellular compartments (somas, dendrites, axons and their terminals) mediate changes in cortical excitability remains unaddressed. Here we consider the acute effects of DCS on excitatory synaptic efficacy. Using multi-scale computational models and rat cortical brain slices, we show the following. (1) Typical tDCS montages produce predominantly tangential (relative to the cortical surface) direction currents (4-12 times radial direction currents), even directly under electrodes. (2) Radial current flow (parallel to the somatodendritic axis) modulates synaptic efficacy consistent with somatic polarization, with depolarization facilitating synaptic efficacy. (3) Tangential current flow (perpendicular to the somatodendritic axis) modulates synaptic efficacy acutely (during stimulation) in an afferent pathway-specific manner that is consistent with terminal polarization, with hyperpolarization facilitating synaptic efficacy. (4) Maximal polarization during uniform DCS is expected at distal (the branch length is more than three times the membrane length constant) synaptic terminals, independent of and two-three times more susceptible than pyramidal neuron somas. We conclude that during acute DCS the cellular targets responsible for modulation of synaptic efficacy are concurrently somata and axon terminals, with the direction of cortical current flow determining the relative influence.
authors.affiliation: Department of Biomedical Engineering, The City College of The City University of New York, Convent Avenue at 140th Street, Steinman Hall, 4th Floor, T-454, New York, NY 10031, USA. asiftr@gmail.com
authors.forename: Asif
authors.initials: A
authors.lastname: Rahman
authors.forename: Davide
authors.initials: D
authors.lastname: Reato
authors.forename: Mattia
authors.initials: M
authors.lastname: Arlotti
authors.forename: Fernando
authors.initials: F
authors.lastname: Gasca
authors.forename: Abhishek
authors.initials: A
authors.lastname: Datta
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Parra
authors.forename: Marom
authors.initials: M
authors.lastname: Bikson
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D009044:Motor Cortex / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission