Abstract
Transcranial direct current stimulation (tDCS) has been reported for its beneficial effects on memory formation and various brain disorders. While the electrophysiological readout of tDCS effects is subtle, astrocytes have been demonstrated to elicit Ca2+ elevations during tDCS in a rodent model. This study aimed to elucidate the effects of tDCS on another major glial cell type, microglia, by histology and in vivo imaging. tDCS performed in awake conditions induced a significant change in the pixel intensity distribution of Iba-1 immunohistochemistry, and microglial somata were enlarged when examined 3 hr after tDCS. These effects were blocked by adrenergic receptor antagonists or in IP3R2 (inositol trisphosphate receptor type 2)-deficient mice, which lack large cytosolic Ca2+ elevations in astrocytes. No obvious changes were observed in isoflurane-anesthetized mice. Furthermore, in vivo two-photon imaging of microglia showed a reduction of motility that was blocked by a beta-2 adrenergic receptor antagonist. Our observations add support for the influence of noradrenaline in tDCS and suggest possible interactions between microglia and astrocytes to express functional changes associated with tDCS.
Significance Statement Transcranial direct current stimulation (tDCS) is a neuromodulation procedure in which a weak electric direct current is delivered through the brain for tens of minutes. Despite reported positive effects, the mechanisms of tDCS stimulation are not yet understood well. Here, we examined microglial morphology in the mouse cortex after tDCS. We find that the morphology and morphological dynamics of microglia are altered by tDCS in a manner dependent on adrenergic receptors, supporting the notion that (nor)adrenergic signaling is involved in tDCS.
Footnotes
Authors report no conflict of interest.
This work was supported by RIKEN BSI and CBS, KAKENHI grants (16H01888, 18H05150, 18K14859), and HFSP (RGP0036/2014).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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