Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain

Abstract

Transcranical direct current stimulation (tDCS) is a treatment known to ameliorate various neurological conditions and enhance memory and cognition in humans. tDCS has gained traction for its potential therapeutic value; however, little is known about its mechanism of action. Using a transgenic mouse expressing G-CaMP7 in astrocytes and a subpopulation of excitatory neurons, we find that tDCS induces large-amplitude astrocytic Ca2+ surges across the entire cortex with no obvious changes in the local field potential. Moreover, sensory evoked cortical responses are enhanced after tDCS. These enhancements are dependent on the alpha-1 adrenergic receptor and are not observed in IP3R2 (inositol trisphosphate receptor type 2) knockout mice, in which astrocytic Ca2+ surges are absent. Together, we propose that tDCS changes the metaplasticity of the cortex through astrocytic Ca2+/IP3 signalling.

Optimizing Transcranial Direct Current Stimulation Protocols to Promote Long-Term Learning

“…Although the effects of tDCS on neural membrane potential have been argued to be small and inconsequential, its effects on glial cells, which comprise ∼50% of brain cells and are sensitive to much smaller depolarizations than neurons, are estimated to fall within a biologically meaningful range (Ruohonen and Karhu 2012). Moreover, glial cells, which secrete many of the same molecules and transmitters as neurons such as calcium and glutamate, play a direct role in learning and synaptic plasticity, thereby providing a tenable mechanism for tDCS to act upon consolidation (see Ben Achour and Pascual 2010; Gibbs et al 2008;Monai et al 2016). Harnessing these latent effects could help mitigate the low reliability found among some studies, particularly the single-session studies that dominate the extant literature, which are not designed to capture delayed consolidation effects.…”

Parkinson's disease treatments: focus on transcranial direct current stimulation (tDCS)

“…However, experimental data do suggest that neurons are sensitive to such weak electric fields, resulting in modulation of action potential firing, synaptic plasticity, and promotion of neurogenesis, [15][16][17] in addition to subtle effects on supporting glial cells. 18,19 One of the experimental benefits of tDCS is the ability to administer a "sham" stimulation that naïve subjects cannot differentiate from "real" stimulation, allowing for the design of controlled studies. This form of placebo is usually achieved by delivering a brief (<30 seconds) ramp current causing a mild subjective sensation over the scalp and then turning the stimulation off.…”

Direct current stimulation modulates LTP and LTD: activity dependence and dendritic effects

“…Previous studies in animals [9]- [14], [70] and humans [71]- [73] have implicated various effects related to synaptic plasticity (NMDAR, BDNF, adenosine, norepinephrine). However, it remains unknown exactly how the DCS electric field interacts with cellular activity to produce these effects.…”

“…Despite the common practice of applying tDCS during training, cellular effects of DCS applied during endogenous plasticity induction remain largely unexplored. Instead, the majority of research has analyzed effects when DCS precedes plasticity induction [9]- [11], or is paired with endogenous activity otherwise not known to induce plasticity [12]- [14]. Here we are interested in the effects of DCS applied during training, i.e.…”