Understanding Neuromodulation Pathways in tDCS: Brain Stem Recordings in Rat During Trigeminal Nerve Direct Current Stimulation

BackgroundRecent evidence suggests that transcranial direct current stimulation (tDCS) indirectly influences brain activity through cranial nerve pathways, particularly the trigeminal nerve. However, the electrophysiological effects of direct current (DC) stimulation on the trigeminal nerve (DC-TNS) and its impact on trigeminal nuclei remain unknown. These nuclei exert control over brainstem centers regulating neurotransmitter release, such as serotonin and norepinephrine, potentially affecting global brain activity. ObjectivesTo investigate how DC-TNS impacts neuronal activity in the principal sensory nucleus (NVsnpr) and the mesencephalic nucleus of the trigeminal nerve (MeV). MethodsTwenty male Sprague Dawley rats (n=10 each nucleus) were anesthetized with urethane. DC stimulation, ranging from 0.5 to 3 mA, targeted the trigeminal nerves marginal branch. Simultaneously, single-unit electrophysiological recordings were obtained using a 32-channel silicon probe, comprising three one-minute intervals: pre-stimulation, DC stimulation, and post-stimulation. Xylocaine was administered to block the trigeminal nerve as a control. ResultsDC-TNS significantly increased neuronal spiking activity in both NVsnpr and MeV, returning to baseline during the post-stimulation phase. When the trigeminal nerve was blocked with xylocaine, the robust 3 mA trigeminal nerve DC stimulation failed to induce increased spiking activity in the trigeminal nuclei. ConclusionOur results offer initial empirical support for trigeminal nuclei activity modulation via DC-TNS. This discovery supports the hypothesis that cranial nerve pathways may play a pivotal role in mediating tDCS effects, setting the stage for further exploration into the complex interplay between peripheral nerves and neural modulation techniques. HighlightsO_LIDirect current stimulation of the trigeminal nerve (DC-TNS) modulates neural activity in rat NVsnpr and MeV. C_LIO_LIXylocaine administration reversibly blocks the DC-TNS effect on neural responses. C_LIO_LITrigeminal nerve stimulation should be considered a possible mechanism of action of tDCS. C_LI