Vagus nerve stimulation produces a hippocampal formation theta rhythm in anesthetized rats

Broncel, Adam; Bocian, Renata; Kłos-Wojtczak, Paulina; Konopacki, Jan

doi:10.1016/j.brainres.2017.08.030

Cited by 15 publications

(7 citation statements)

References 72 publications

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“…Quite the opposite. The presented data actually indicates the excitation of the hippocampal formation during VNS, as previously suggested [ 30 ]. This suggestion is also supported by earlier findings that VNS potentiates hippocampal LTP and enhances hippocampal synaptic transmission in freely moving and anesthetized rats [ 19 , 20 , 23 ].…”

Section: Discussionsupporting

confidence: 86%

“…This memory processing is related to an increase in the excitation of the hippocampal neuronal network and the presence of a local theta rhythm [ 24 – 29 ]. In agreement with this suggestion, Broncel et al [ 30 ], using several experimental protocols, have recently demonstrated that VNS induced the HPC theta rhythm in anesthetized rats. This was the first direct finding demonstrating the vagal nerve to be involved in central mechanisms underlying oscillations and synchrony in limbic cortex.…”

Section: Introductionsupporting

confidence: 59%

“…The basic experimental model used in the present study to evaluate the central effect of VNS was HPC type II theta rhythm recorded in urethanized rats. We have recently provided the first evidence that, using different protocols and current pulse parameters, VNS produced a very well synchronized HPC type II theta [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Based on our previous experiments [ 30 ], in the present study, the following square pulse parameters were applied: pulse duration (1 ms), train duration (10 s), frequency (10 Hz) and current intensity of 8 mA. These VNS parameters were previously found to induce a direct, brief effect on HPC field potential, i.e., theta rhythm appearing during vagal stimulation.…”

Section: Methodsmentioning

confidence: 99%

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Medial septal cholinergic mediation of hippocampal theta rhythm induced by vagal nerve stimulation

et al. 2018

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BackgroundElectrical vagal nerve stimulation (VNS) has been used for years to treat patients with drug-resistant epilepsy. This technique also remains under investigation as a specific treatment of patients with Alzheimer’s disease. Recently we discovered that VNS induced hippocampal formation (HPC) type II theta rhythm, which is involved in memory consolidation. In the present study, we have extended our previous observation and addressed the neuronal substrate and pharmacological profile of HPC type II theta rhythm induced by VNS in anesthetized rats.MethodsMale Wistar rats were implanted with a VNS cuff electrode around the left vagus nerve, a tungsten microelectrode for recording the HPC field activity, and a medial septal (MS) cannula for the injection of a local anesthetic, procaine, and muscarinic agents. A direct, brief effect of VNS on the HPC field potential was evaluated before and after medial-septal drug injection.ResultsMedial septal injection of local anesthetic, procaine, reversibly abolished VNS-induced HPC theta rhythm. With the use of cholinergic muscarinic agonist and antagonists, we demonstrated that medial septal M1 receptors are involved in the mediation of the VNS effect on HPC theta field potential.ConclusionThe MS cholinergic M1 receptor mechanism integrates not only central inputs from the brainstem synchronizing pathway, which underlies the production of HPC type II theta rhythm, but also the input from the vagal afferents in the brain stem.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Medial septal cholinergic mediation of hippocampal theta rhythm induced by vagal nerve stimulation

et al. 2018

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“…In the rat hippocampus, VNS resulted in increased volume, 39 expression of neurotrophic growth factors, 40 neuronal plasticity and cell proliferation, 40,41 synaptic transmission, 42 blood flow, 43 and local theta rhythms. 44 In addition, VNS appears to enhance memory in both rats and humans, likely due to increased activation of hippocampal circuitry. 45 In the amygdala, VNS has been shown to enhance neuroplasticity, 46 increase neuronal activity and excitatory synaptic transmission, 47 and increase regional blood flow.…”

Section: Limbic Circuitrymentioning

confidence: 99%

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation

Mithani

Mikhail

Morgan

et al. 2019

Annals of Neurology

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Objective: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. Methods: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. Results: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). Interpretation: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753 N early one-third of children with epilepsy are refractory to medications. 1,2 Persistent seizures are associated with mortality, disability, psychosocial isolation, and diminished quality of life. 3-6 Vagus nerve stimulation (VNS) is an effective, safe, and well-tolerated intervention for a subset of patients with treatment-resistant epilepsy. 7-10 Although the goal of VNS is not complete resolution of seizures, many children will show a significant reduction in seizure frequency, as well as a reduction in hospitalizations and psychosocial comorbidities. 11,12 View this article online at wileyonlinelibrary.com.

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