RESUMEN
Transcranial 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 circuits in 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.
RESUMEN
Transcranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. On the other hand, 20 min of cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these after effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated versus non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and after effects of tDCS, as well as the asymmetric after effects induced by anodal and cathodal stimulation.
