Table 1.
Summary of DCS studies conducted in animal and human brain cells and brain slices. 4-AP: 4-aminopyridine; ACC: anterior cingulate cortex; CA1: cornu ammonis 1; d: diameter; DCS: direct current stimulation; ESC: embryonic stem cell; EPSC: excitatory postsynaptic currents; fEPSP: field excitatory postsynaptic potential; KA: kainic acid; l: length; LII/III, V: Layer 2/3, 5; LTP: long-term potentiation; LTD: long-term depression; MUA: multiunit activity; NMDA: N-methyl-D-aspartate; DBS: deep brain stimulation; N/A: not available; MEA: multi-electrode array; mGluR5-mTOR: metabotropic glutamate receptor subunit 5—mechanistic target of rapamycin; NPCs: neural precursor cells; RAB3A: Ras-related protein; TBS: theta burst stimulation; qRT-PCR: quantitative real-time polymerase chain reaction.
| Reference | Origin | Tissue | Stimulation Duration (min) | Field Strength (mV/mm) | Electrode Size (mm) | Current Strength (µA) | Slice Orientation |
Readout | Results/Observations |
|---|---|---|---|---|---|---|---|---|---|
| Kronberg et al., 2017 [47] | Rat | Hippocampal slices | 0.75, 3, 15 and 30 | 20 | 1 d, 12 l | 100–200 | Parallel to somato-dendritic axis of CA1 pyramidal neurons | Recording of fEPSP before and after plasticity induction with low and high frequency suprathreshold electrical stimuli combined with DCS | Cathodal DCS enhances LTP in apical dendrites; anodal enhances LTP in basal dendrites; both reduce LTD in apical dendrites; no effect in weakly active synapses or during NMDA receptor block |
| Rahman et al., 2017 [48] | Rat | Motor cortex slices | 0.05–0.08 | 10–20 | N/A | 10–150 | Orthodromic stimulation of LII/III | Recording of fEPSPs | Presynaptic inputs were delivered with constant or Poisson-distributed stimuli prior to single DCS stimuli; postsynaptic voltage response during DCS and ongoing presynaptic activity results in sustained and cumulative changes in fEPSP; regulated by synaptic efficacy, number of active inputs, and rate of presynaptic activity |
| Chakraborty et al., 2018 [49] | Mouse | Coronal pre- frontal cortical slices | 1 | 5 | N/A | 58.3–34.8 | Parallel and orthogonal to dendrito-axonic axis of L-V pyramidal cells | Recording of membrane polarization per V/m of effective electric field | Suprathreshold stimulation (important for e.g., DBS) induces action potentials at terminals; subthreshold stimulation (important for DCS) modulates synaptic efficacy of axon terminal polarization; significant effect after parallel-, no effect after orthogonal orientated polarization |
| Kronberg et al., 2020 [21] | Rat | Hippocampal slices | 0.06 | 20 | 1 d, 12 l | 100–200 | Parallel to somato-dendritic axis of CA1 pyramidal neurons | Recording of fEPSPs | Anodal DCS boosts LTP of Hebbian plasticity-dependent pathways during the induction of LTP with TBS |
| Latchoumane et al., 2018 [50] | Mouse | ESC-derived neuron and glial cells | 15, (5 days) day 14 cathodal, day 15–19 anodal | N/A | N/A | 10 | / | qRT-PCR analysis after chronic DCS on ESC-derived neurons after L-Glutamate administration | Upregulation of NMDA receptor subunit NR2A, and RAB3A in mouse Hb9 ESC-derived neuronal and glial cells |
| Ranieri et al., 2012 [51] | Rat | Hippocampal slices | 20 | N/A | 9 d | 200–250 | Parallel to soma-dendritic axis of CA1 pyramidal cells | Recording of fEPSPs; recordings of gene induction | Anodal DCS up-, while cathodal DCS downregulates LTP induced by TBS; induction of early genes c-fos and Zif268 following neuronal activation |
| Chang, Lu, and Shyu, 2015 [20] | Mouse | Thalamocingulate slices | 15 | 4 | N/A | 400 | Parallel and perpendicular to direction of axodendritic fibers in the ACC | EPSCs in MEA and patch recordings | Cathodal DCS induces LTD via an NMDA-dependent mechanism |
| Sun et al., 2016 [18] | Mouse, Human | Coronal slices | 10 or 25 | 8.18 or 10.18 | 1 d, 3 l | 300 or 400 | Parallel or orthogonal to the M1 fibers (L V to II/III projections) | Recording of fEPSPs, mGluR5-mTOR signaling as novel pathway in tDCS | Cathodal DCS induces LTD in both human and mouse cortex in vitro |
| Sun et al., 2020 [52] | Mouse, Human | Cortical slices | 25 | 2.3 | 1 d, 3 l | 400 | Orthogonal to pia, parallel to vertical interlayer M1 projections; cathode proximal to cortical pia surface; anode beneath subcortical white matter | Recording of fEPSPs; immune-staining; KA-induced seizure model | DCS induced LTD-like plasticity in superficial cortical layers, and LTP-like plasticity in deep cortical layers; regional depression of cortical excitability is NMDA-dependent |
| Reato, Bikson, and Parra, 2015 [53] | Rat | Hippocampal slices | 10 | −20 to + 20 | N/A | N/A | Parallel to CA3 pyramidal neurons | Changes in gamma power; MUA measurement | Induction of gamma oscillations by carbachol prior to DCS; altered gamma power and MUA after DCS; acute upregulation of MUA and power at positive fields; acute downregulation at negative fields |
| Zhao et al., 2015 [54] | Mouse | NPCs | 90 | 115 | 1 d | 0.25 nA | / | Migration assay | DC electric fields enhance cellular mobility; cell migration to the cathode via a calcium-dependent mechanism |