Entrainment of cerebellar purkinje cells with directional AC electric fields in anesthetized rats

Abstract

Background: Transcranial electrical stimulation (tES) shows promise to treat neurological disorders. Knowledge of how the orthogonal components of the electric field (E-field) alter neuronal activity is required for strategic placement of transcranial electrodes. Yet, essentially no information exists on this relationship for mammalian cerebellum in vivo, despite the cerebellum being a target for clinical tES studies. Objective: To characterize how cerebellar Purkinje cell (PC) activity varies with the intensity, frequency, and direction of applied AC and DC E-fields. Methods: Extracellular recordings were obtained from vermis lobule 7 PCs in anesthetized rats. AC (2 e100 Hz) or DC E-fields were generated in a range of intensities (0.75e30 mV/mm) in three orthogonal directions. Field-evoked PC simple spike activity was characterized in terms of firing rate modulation and phase-locking as a function of these parameters. t-tests were used for statistical comparisons. Results: The effect of applied E-fields was direction and intensity dependent, with rostrocaudally directed fields causing stronger modulations than dorsoventral fields and mediolaterally directed ones causing little to no effect, on average. The directionality dependent modulation suggests that PC is the primary cell type affected the most by electric stimulation, and this effect was probably given rise by a large dendritic tree and a soma. AC stimulation entrained activity in a frequency dependent manner, with stronger phase-locking to the stimulus cycle at higher frequencies. DC fields produced a modulation consisting of strong transients at current onset and offset with an intervening plateau. Conclusion: Orientation of the exogenous E-field critically determines the modulation depth of cerebellar cortical output. With properly oriented fields, PC simple spike activity can strongly be entrained by AC fields, overriding the spontaneous firing pattern.

Epidural cerebellar stimulation drives widespread neural synchrony in the intact and stroke perilesional cortex

“…Recent work that stimulated the cerebellum using transcranial alternating current showed that multiunit activity of the cerebellar cortex was enhanced during the negative phase of stimulation, while the positive phase suppressed activity [37,47]. This work also showed that Purkinje cells were the main cell type that was affected by transcranial epidural cerebellar stimulation [37]. Similarly, anodal DCS over the cerebellum has been shown to have a 'smoothing' effect on corticomotor maps [24].…”

“…These results demonstrated that subjects showed subsequent improvements in motor behavior, and changes in MEPs, axonal growth protein and synaptogenetic markers in peri-infarct cortices [34][35][36]. Other animal work has shown that epidural stimulation of the cerebellum has a smoothing effect on corticomotor maps [24], and that cerebellar transcranial electric stimulation (tES) can entrain neurons in the cerebellar cortex and exerts its effects principally through modulation of Purkinje cells [37].…”

“…The second screw was placed 14 mm posterior and 3.0 mm lateral to bregma. This arrangement mimics a rostrocaudally oriented electric field, which has been shown to result in the greatest amount of Purkinje cell modulation [37,47]. Our stimulation electrode montage roughly encompassed the posterior lobe of the cerebellum; the anterior bone screw was connected to the cathode (current magnitude: − 175 μA), and the posterior screw served as the ground (Fig.…”

“…Meanwhile, cathodal epidural stimulation has the reverse effect [24]. New work recently showed that epidural cerebellar stimulation principally affects the main inhibitory cell in the cerebellar cortex, the Purkinje cell [37]. The cerebellar cortex strongly inhibits the cerebellar nuclei.…”

A randomized controlled trial to explore the efficacy and safety of transcranial direct current stimulation on patients with post-stroke fatigue

“…Ciechanski et al [ 42 ] found that tDCS could enhance neuronal connections with a long-term enhancement mechanism by increasing neuronal spontaneous discharge and synaptic efficiency. However, recent study [ 43 ] have shown that under the stimulation intensity commonly used in the study, tDCS had no systematic effect on discharge rate or discharge pattern. Subtle but statistically insignificant changes occur only in sites with the most sensitivity or the highest intensity of anodic stimulation, which suggested that the effects of tDCS observed in previous study were likely to occur through mechanisms other than direct neuronal depolarization.…”