RT Journal Article
SR Electronic
T1 Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.02.18.529047
DO 10.1101/2023.02.18.529047
A1 Sánchez-León, Carlos A
A1 Sánchez-Garrido Campos, Guillermo
A1 Fernández, Marta
A1 Sánchez-López, Alvaro
A1 Medina, Javier F
A1 Márquez-Ruiz, Javier
YR 2024
UL http://biorxiv.org/content/early/2024/06/21/2023.02.18.529047.abstract
AB 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 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 Purkinje cells (PC) 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.Competing Interest StatementThe authors have declared no competing interest.