Entrainment of Cerebellar Nuclear Cells via AC Stimulation of the Cerebellar Cortex

Transcranial alternating current stimulation (tACS) is a non-invasive neuromodulation technique that is being tested for treatment of a variety of neural disorders. Animal studies investigating the underlying mechanisms of tACS are scarce. In the present study, we have applied sinusoidal alternating currents (AC) from 10 Hz to 400 Hz to the cerebellar cortex in ketamine/xylazine anesthetized rats, as this has been previously shown to modulate and entrain Purkinje cell (PC) simple spike activity. The activity of cerebellar nuclear (CN) cells, projected by the PCs, were recorded with microelectrodes during stimulation. The results demonstrate that CN cell spiking activity can be entrained indirectly via PC modulation at the frequency of the AC stimulation. Interestingly, unlike in the case of PCs, there is a tuning curve for modulation where the frequencies in the midrange are more effective. The peak frequency of the tuning curve varies between the cells, potentially due to differences in electrophysiological properties of the cellular subtypes. These results agree with human trials of cerebellar tACS where the functional impact of the intervention was frequency dependent.