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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 Ca 2+  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 IP 3 R2 (inositol trisphosphate receptor type 2) knockout mice, in which astrocytic Ca 2+  surges are absent. Together, we propose that tDCS changes the metaplasticity of the cortex through astrocytic Ca 2+ /IP 3  signalling.

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