Transcranial Direct Current Stimulation (tDCS) Induces Adrenergic Receptor-Dependent Microglial Morphological Changes in Mice.

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 h 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 β2-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.