Direct Current Stimulation in Cell Culture Systems and Brain Slices—New Approaches for Mechanistic Evaluation of Neuronal Plasticity and Neuromodulation: State of the Art

Abstract

Non-invasive direct current stimulation (DCS) of the human brain induces neuronal plasticity and alters plasticity-related cognition and behavior. Numerous basic animal research studies focusing on molecular and cellular targets of DCS have been published. In vivo, ex vivo, and in vitro models enhanced knowledge about mechanistic foundations of DCS effects. Our review identified 451 papers using a PRISMA-based search strategy. Only a minority of these papers used cell culture or brain slice experiments with DCS paradigms comparable to those applied in humans. Most of the studies were performed in brain slices (9 papers), whereas cell culture experiments (2 papers) were only rarely conducted. These ex vivo and in vitro approaches underline the importance of cell and electric field orientation, cell morphology, cell location within populations, stimulation duration (acute, prolonged, chronic), and molecular changes, such as Ca2+-dependent intracellular signaling pathways, for the effects of DC stimulation. The reviewed studies help to clarify and confirm basic mechanisms of this intervention. However, the potential of in vitro studies has not been fully exploited and a more systematic combination of rodent models, ex vivo, and cellular approaches might provide a better insight into the neurophysiological changes caused by tDCS.

On-chip brain slice stimulation: precise control of electric fields and tissue orientation

“…In vitro tDCS studies, which will be referred to as (t)DCS studies in this manuscript, on both the single neuron and neural network levels have shown weak EFs at subthreshold magnitudes can elevate neural membrane potential to shorten spike timing and increase the firing rate of an active neuron. [22][23][24][25] The EF intensity, 23,26 the relative orientation between EF and the neural somato-dendritic axis, [27][28][29][30] as well as the background activity level of the neural network, 31 all lead to different extents of membrane potential polarization and the yielding aftereffects. Most of these in vitro studies were performed in acute brain slices on electrophysiological setups, where a fluidic perfusion system was integrated to maintain cell viability and parallel silver-silver chloride (Ag/AgCl) electrodes were adopted to generate the EF.…”

Brain stimulation-on-a-chip: a neuromodulation platform for brain slices

“…These studies, conducted on single neurons and neural networks, have demonstrated that weak EFs at subthreshold levels can depolarize neural membrane potential, leading to reduced spike timing and heightened firing rates in active neurons. [22][23][24][25] The EF intensity, 23,26 the relative orientation between EF and the neural somatodendritic axis, [27][28][29][30] as well as the background activity level of the neural network, 31 all lead to different extents of membrane potential polarization and the yielding aftereffects. Most of these in vitro studies were performed in acute brain slices on electrophysiological setups, where a fluidic perfusion system was integrated to maintain cell viability and parallel silver-silver chloride (Ag/AgCl) electrodes were adopted to generate the EF.…”

Kalziumabhängige Effekte nikotinerger Modulation LTD-ähnlicher Neuroplastizität im Menschen mittels kathodaler tDCS

“…Dies gilt insbesondere, da die Wirkmechanismen auf zellulärer Ebene nicht direkt gemessen, sondern lediglich indirekt aus den Veränderungen der MEP-Amplituden und unter Heranziehung anderer Studien abgeleitet wurden. Weitere Studien, auch im tierexperimentellen Bereich, sind notwendig, um die hier genannten Ergebnisse zu erhärten (Euskirchen et al 2021). Während die Durchführung einer solchen Studie im Menschenmodell deutliche Vorteile bezüglich der etwaigen klinischen Relevanz bringt, so entsteht jedoch auch eine höhere Variabilität.…”