Publication Date
4-14-2025
Journal
eLife
DOI
10.7554/eLife.100941
PMID
40228055
PMCID
PMC11996176
PubMedCentral® Posted Date
4-14-2025
PubMedCentral® Full Text Version
Post-print
Abstract
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. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n=9) were prepared for the chronic recording of local field potentials (LFPs) to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n=24) and anesthetized (n=27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n=8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n=6). In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of PCs and non-PC in the mouse cerebellar cortex. 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 highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.
Keywords
Animals, Purkinje Cells, Transcranial Direct Current Stimulation, Mice, Wakefulness, Action Potentials, Dendrites, Cerebellar Cortex, Mice, Inbred C57BL, Male
Published Open-Access
yes
Recommended Citation
Sánchez-León, Carlos A; Sánchez-Garrido Campos, Guillermo; Fernández, Marta; et al., "Somatodendritic Orientation Determines tDCS-Induced Neuromodulation of Purkinje Cell Activity in Awake Mice" (2025). Faculty and Staff Publications. 5297.
https://digitalcommons.library.tmc.edu/baylor_docs/5297