Trigeminal nerve direct current stimulation modulates raphe-hippocampal network synchrony in rats

Area of Science:

• Neuroscience
• Neuromodulation
• Cognitive Science

Background:

• Trigeminal nerve stimulation (TNS) offers a noninvasive approach to modulate subcortical circuits crucial for cognition.
• This study examines the impact of trigeminal nerve direct current stimulation (TN-DCS) on neuronal activity and raphe-hippocampal coherence.

Purpose of the Study:

• To investigate the effects of TN-DCS on neuronal firing rates and synchronization between the raphe nuclei and hippocampus.
• To determine the cell-type specificity and amplitude dependence of TN-DCS effects.
• To elucidate the role of trigeminal input and serotonergic signaling in mediating TN-DCS outcomes.

Main Methods:

• Rats underwent surgical implantation of silicon probes for simultaneous recording from the hippocampus and either the dorsal raphe nucleus (DRN) or median raphe nucleus (MnRN).
• Direct currents (0.25–3 mA) were applied to the trigeminal nerve during 3-minute stimulation sessions.
• Neuronal activity and local field potentials were analyzed during pre-, during, and post-stimulation periods.

Main Results:

• TN-DCS rapidly and reversibly altered neuronal firing in the DRN, MnRN, and hippocampus in a cell-type and amplitude-dependent manner.
• Putative non-serotonergic raphe neurons showed increased firing rates, while putative serotonergic neurons exhibited inconsistent changes.
• TN-DCS enhanced theta-band synchrony between non-serotonergic raphe neurons and hippocampal activity, an effect blocked by trigeminal nerve block or serotonergic agonists.

Conclusions:

• TN-DCS dynamically modulates raphe-hippocampal firing and theta synchrony through amplitude-dependent mechanisms.
• The observed effects necessitate intact trigeminal input and functional serotonergic signaling.
• TN-DCS shows potential as a targeted neuromodulation strategy for cognitive and mood disorders.