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INTRODUCTION: Vagal nerve stimulation (VNS) is currently approved for treatment of both pharmacologically resistant seizures and severe refractory depression. In addition, VNS is used for treatment of Alzheimer disease, schizophrenia and central inflammation. Interestingly, VNS has also been demonstrated to enhance HPC-induced long-term potentiation (LTP) and improve memory in rats and humans. The above mentioned findings suggest the direct involvement of hippocampal formation (HPC) theta rhythm. AIM(S): We have just recently documented for the first time the presence of HPC type II theta in response to the application of VNS. VNS-induced theta rhythm appeared in different experimental protocols and, depending on the current intensity, could occur directly during VNS (brief effect) or after vagal stimulation (delayed effect). The aim of the present study was to demonstrate that the effect of left VNS on HPC theta rhythm is mediated by medial septum. METHOD(S): Anesthetized rats were implanted with vagal cuff electrodes and unilaterally with HPC recording tungsten electrode. The VNS (8 mA, 500 us, 10 s) were applied three times: before HPC injection of procaine (control), 10 min after and 60 min after. The EEG signals were analyzed off‑line using the Spike‑2 software computing system (Cambridge Electronic Design, Cambridge, UK). RESULTS: We demonstrated that medial-septal procaine injection reversibly abolished HPC type II theta rhythm induced by VNS in anesthetized rats. CONCLUSIONS: We believe that the present findings concerning type II theta rhythm open a new perspective into the study of vagal nerve involvement in central processes of sensory-motor integration, cognition and memory.
INTRODUCTION: A number of invasive and noninvasive brain‑stimulation techniques are used in clinical neurology. Stimulation of peripheral nerves may affect brain activity through a bottom-up mechanism, for instance, by stimulating cranial nerve nuclei in the brainstem. With specific regard to peripheral methods, studies using vagal nerve stimulation (VNS) have demonstrated that neurostimulation modalities can produce robust therapeutic effects without incurring unsafe consequences on brain function. Just recently, we have demonstrated that direct VNS induced hippocampal (HPC) theta rhythms. The fact that HPC theta rhythm is directly involved in memory processing suggests that VNS can be considered as a useful treatment of patients with Alzheimer’s disease. METHOD(S): Transcutaneous stimulation of the vagus nerve (t-VNS) was performed on the level of external ear in anesthetized rats. Two uninsulated tungsten electrodes (0.1‑0.2 kΩ) were used for bipolar VNS through the left lobule of the auricle. Three different points localized on the left lobule of the auricle were tested. The following VNS intensities were applied: 0.2‑10 mA. The frequency of VNS was in range (5‑60 Hz), pulse duration (1 ms) and train duration (10 s). RESULTS: Three separate points of localized on the left lobule of the auricle responded with different HPC field responses. The most effective in inducing HPC theta rhythm was the area of entrance of the external auditory canal. CONCLUSIONS: The data obtained in the project indicated that the entrance of external auditory canal was found to be the most effective in inducing theta rhythm during t‑VNS. Further, the effectiveness of t‑VNS on HPC theta rhythm is determined by its intensity and local density of vagal endings. FINANCIAL SUPPORT: These studies were supported by The National Centre of Research and Development (grant no 01.02.00‑00‑0023/17‑001).
Neuromodulation is a therapeutic technique that involves modification of neural function via external stimulation, usually in the form of electrical impulses. Prominent examples of neuromodulative therapies include vagus nerve stimulation for epilepsy, Alzheimer’s disease, and even deep brain stimulation for Parkinson’s disease. Trigeminal nerve stimulation (TNS) has also been applied as a therapeutic tool in a variety of disease processes and has shown efficacy in the treatment of epilepsy and depression. AIM(S): The aim of the present study was to evaluate if transcutaneous TNS (t-TNS) could affect the hippocampal EEG activity. METHOD(S): Male Wistar rats were implanted with a tungsten microelectrode for recording hippocampal formation (HPC) field activity. Furthermore, two uninsulated tungsten electrodes were used for t-TNS in eye‑ear line in anesthetized rats. The stimulation was conducted at three point: closer to the eye (point 1), in the middle of line eye-ear (point 2), and closer to the ear (point 3). The following t‑TNS intensities ware tested: 4, 6, 8, and 10 mA. The remaining parameters of stimulation were constant: pulse duration (1 ms), train duration (10 s), frequency (10 Hz). RESULTS: Stimulation only in the point closer to the ear and in the eye-ear line was found to be productive in inducing nicely developed and well-synchronized hippocampal theta rhythm. However, t‑TNS in the range below 6 mA was found to be subthreshold (theta rhythm was not observed in HPC). Theta activity was observed at point 3 during stimulation only when the intensity of stimulation was equal or higher than 6 mA. CONCLUSIONS: Only the point located closer to the ear in the eye-ear line was found to be effective in inducing t‑TNS theta rhythm. The effectiveness of t‑TNS on hippocampal theta rhythm was determined by its intensity and density of trigeminal nerve endings. FINANCIAL SUPPORT: These studies were supported by The National Centre of Research and Development (grant no. 01.02.00‑00‑0023/17‑001).
Vagal nerve stimulation (VNS) refers to any tech‑ nique that stimulates the vagal nerve, including man‑ ual or electrical stimulation. Approved by the FDA at the end of the 20th century, VNS was initially used as an add-on treatment for medically refractory epilep‑ sy. Today, VNS has also been studied as a treatment for mood and cognitive disorders, such as major depression, bipolar disorder, and Alzheimer’s disease. Although VNS requires an invasive surgical procedure, this technique is increasingly widespread in medical practice. Recent‑ ly, we have demonstrated that hippocampal (HPC) thetarhythm can be produced, depending on current inten‑ sity, directly during vagal nerve stimulation (VNS) or post-stimulation. This suggests that theta EEG pattern can be used as a bio-indicator of the efficiency of VNS. In the present study, we focused on three specific tech‑ nical issues related to the stimulation procedure of the vagal nerve: 1) Does the type of electrode used for VNS and the technique of its implantation affect the param‑ eters of the HPC theta rhythm? 2) Does the type of elec‑ trode used determine the current intensity threshold of VNS-induced HPC theta? 3) Is the repeatability of the VNS effect determined by the type of electrode used? In rats (male Wistar) with an implanted tungsten micro‑ electrode (0.1–0.9 MΩ) for recording the HPC field ac‑ tivity, VNS was applied using two types of stimulating electrodes: tungsten bipolar fork electrode and plati‑ num-iridium cuff electrode. The first type of stimulating electrode touched a vagal nerve surface only during the stimulation and the second type surrounded the nerve and has contact with it throughout the entire experi‑ ment. During experiments the following VNS intensi‑ ties were tested: 1, 2, 4, 6, 8, and 10 mA. The remaining parameters were constant: pulse duration (1 ms), train duration (10 s), and frequency (10 Hz). A direct (brief) effect of VNS on the HPC field potential was evaluated. We demonstrated that using the cuff electrode for VNS offers a lower current intensity threshold for inducing HPC theta than using a fork electrode. Furthermore, in contrast to a fork electrode, the cuff electrode offers re‑ peatability of the VNS effect on HPC theta activity. The final effect of VNS is determined by many factors in‑ cluding the stimulation protocol and type of stimulating electrode used. This work was supported by RPO grant (RPLD.01.02.02-10-0067/17-00)
INTRODUCTION: Hippocampal (HPC) theta rhythm may be important for various phenomena, including attention and acquisition of sensory information. Two types of HPC theta (types I and II) exist based on pharmacological, behavioral, and electrophysiological properties. Both types occur in conscious animals, whereas only type II (atropine-sensitive) theta is present under anaesthesia. The circuit of HPC theta synchronization includes the medial septum-diagonal band of Broca (MSDB), with cholinergic and GABA-ergic neurons comprising the two main projections from MSDB to HPC. Just recently we have demonstrated that vagal nerve stimulation (VNS) induces HPC type II theta in urethanized rats. AIM(S): The primary aim of the present study was to assess the effects of cholinergic MSDB inhibition on VNS induced HPC theta rhythm. METHOD(S): Anesthetized rats were implanted with vagal bipolar cuff electrode. VNS parameters were constant: pulse duration (1.0 ms), train duration (10 s), frequency (10 Hz) and pulse intensity 8 mA. Monopolar tungsten electrodes were implanted into HPC in accordance to standard stereotactic technique. HPC field potential was analyzed of off‑line using the Spike‑2 software computing system (CED, Cambridge, UK). In a separate experiments cholinergic, surface only during stimulation. VNS intensity was tested in a range: 0.2–10.0 mA. Remaining parameters were constant: pulse duration (1.0 ms), train duration (10 s), frequency (10 Hz). RESULTS: We demonstrated that the chronically implanted vagal cuff electrode decreased (vs tungsten electrode) the amplitude of HPC type II theta in 30%. The effect of different types of electrodes used for VNS was also noticed in the evaluation of HPC theta threshold. CONCLUSIONS: The type of the stimulation electrode (cuff vs. tungsten) used determines the final effect of VNS on hippocampal field potential.
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