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

Abstract

AbstractTranscranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuitsin vivo. In this study, we observe that tDCS induces a heterogeneous polarity-dependent 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 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, enhance the reliability of current stimulation protocols and optimize desired effects in basic and clinical human applications.