Asamoah, B. | bioRxiv Science

bioRxiv2023

Trigeminal nerve direct current stimulation causes sustained increase in neural activity in the rat hippocampus

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation method that can modulate many brain functions including learning and memory. Recent evidence suggests that tDCS memory effects may be caused by co-stimulation of scalp nerves such as the trigeminal nerve (TN), and not the electric field in the brain. The TN gives input to brainstem nuclei, including the locus coeruleus that controls noradrenaline release across brain regions, including hippocampus. However, the effects of TN direct current stimulation (TN-DCS) are currently not well understood. In this study we hypothesized that TN-DCS manipulates hippocampal activity via an LC-noradrenergic bottom-up pathway. We recorded neural activity in rat hippocampus using multichannel silicon probes. We applied 3 minutes of 0.25 mA or 1 mA TN-DCS, monitored hippocampal activity for up to 1 hour and calculated spikes-rate and spike-field coherence metrics. Subcutaneous injections of xylocaine were used to block TN and intraperitoneal injection of clonidine to block the LC pathway. We found that 1 mA TN-DCS caused a significant increase in hippocampal spike-rate lasting 45 minutes in addition to significant changes in spike-field coherence, while 0.25 mA TN-DCS did not. TN blockage prevented spike-rate increases, confirming effects were not caused by the electric field in the brain. When 1 mA TN-DCS was delivered during clonidine blockage no increase in spike-rate was observed, suggesting an important role for the LC-noradrenergic pathway. These results provide a neural basis to support a tDCS TN co-stimulation mechanism. TN-DCS emerges as an important tool to potentially modulate learning and memory. HighlightsO_LITrigeminal nerve direct current stimulation (TN-DCS) boosts hippocampal spike rates C_LIO_LITN-DCS alters spike-field coherence in theta and gamma bands across the hippocampus. C_LIO_LIBlockade experiments indicate that TN-DCS modulated hippocampal activity via the LC-noradrenergic pathway. C_LIO_LITN-DCS emerges as a potential tool for memory manipulation. C_LI Figure Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/571341v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@d60a69org.highwire.dtl.DTLVardef@4598daorg.highwire.dtl.DTLVardef@1363f89org.highwire.dtl.DTLVardef@856b2e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

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

neuroscience↗