Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice

Transcranial direct-current stimulation (tDCS) is a promising non-invasive neuromodulatory technique being proposed for treating neurologic disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. In this study, we observe a heterogeneous polarity modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. Using a combination of juxtacellular labeling and high-density Neuropixels recordings, we demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be fully explained by taking into account the somatodendritic orientation relative to the electric field. Our findings emphasize the importance of considering neuronal orientation and morphological aspects to increase the predictive power of tDCS computational models and optimize desired effects in basic and clinical human applications.