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

Nadine Euskirchen,Michael A. Nitsche,Christoph van Thriel

doi:10.3390/cells10123583

Nadine Euskirchen, Michael A. Nitsche + Show 1 more

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https://doi.org/10.3390/cells10123583

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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.

Highlights

Effects of tDCS are supposed to be accomplished by a subthreshold modulation of neuronal membrane resting potentials that alters cortical excitability, and can subsequently induce more enduring effects related to neuroplasticity [3]
For the primary motor cortex model in humans, stimulation with the anode placed over the motor cortex target and a cathodal return electrode positioned over the contralateral supraorbital area increased motor evoked potentials (MEPs) (long-term potentiation (LTP)-like mechanism) and reversed electrode positioning reduced MEPs (long-term depression (LTD)-like mechanism) [3,4,5]
To explore the mechanisms of action of this intervention in detail, ex vivo and in vitro direct current stimulation (DCS) studies are important to unravel the mechanistic foundations of the impact of tDCS on cells, cell compartments, and molecular physiology

Summary

Introduction

The targeted modulation of brain activity via controlled magnetic or electric stimulation is a valuable research tool in neuroscience, as well as an emerging clinical intervention in neurological and psychiatric diseases [1]. Dependent on the stimulation protocol, the intervention induces acute, and prolonged, shifts of cortical excitability [3,4,5]. Effects of tDCS are supposed to be accomplished by a subthreshold modulation of neuronal membrane resting potentials that alters cortical excitability, and can subsequently induce more enduring effects related to neuroplasticity [3]. It was shown that tDCS effects depend on the current flow direction in relation to the targeted neuron populations or brain regions [3,7,8]. With other return electrode positions, no clear physiological effects emerged [3]

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