Review
The chemical neuroanatomy of vagus nerve stimulation

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Abstract

In this short overview a reappraisal of the anatomical connections of vagal afferents is reported. The manuscript moves from classic neuroanatomy to review details of vagus nerve anatomy which are now becoming more and more relevant for clinical outcomes (i.e. the therapeutic use of vagus nerve stimulation). In drawing such an updated odology of central vagal connections the anatomical basis subserving the neurochemical effects of vagal stimulation are addressed. In detail, apart from the thalamic projection of central vagal afferents, the monoaminergic systems appear to play a pivotal role. Stemming from the chemical neuroanatomy of monoamines such as serotonin and norepinephrine the widespread effects of vagal stimulation on cerebral cortical activity are better elucidated. This refers both to the antiepileptic effects and most recently to the beneficial effects of vagal stimulation in mood and cognitive disorders.

Research highlights

▶ Vagus nerve stimulation activates the nucleus of the solitary tract. ▶ Efficacy of vagus nerve stimulation relies on the integrity of locus coeruleus. ▶ Efficacy of vagus nerve stimulation relies on effects produced by norepinephrine. ▶ Efficacy of vagus nerve stimulation is long-lasting and plasticity-dependent.

Section snippets

Origin and peripheral course

The vagus nerve, once named pneumogastric nerve, is the tenth and the longest of the cranial nerves. Its name derives from Latin root, “wandering”, as consequence of its long course, from the brain stem to the abdomen. The vagus nerve arises from the medulla and possesses numerous rootlets, between the inferior olive and the inferior cerebellar peduncle, in series with the glossopharyngeal nerve above and the accessory nerve (Wiles et al., 2007). The rootlets form a single trunk, which leaves

The background of vagus nerve stimulation

The vagus nerve stimulation (VNS) was proposed in late 19th for the treatment of epilepsy by the American neurologist Corning, 1882, Corning, 1883. This was based on the idea that seizures may be due to alterations in cerebral blood flow. Accordingly, seizures were previously associated with facial flushing and bounding carotid and cranial pulse as an excess of cerebral blood flow (Parry, 1792). In keeping with this, it was reported that the decrease of cerebral blood flow following manual

Fiber types and the electrical stimulation of the vagus nerve

Myelination of the human vagus nerve begins between 14 and 17 weeks postconception (pc) and the number of myelinated fibers augments from about 5000 at 26 weeks pc to as many as 40,000, the adult value, at 10 weeks after birth (Wozniak and O’Rahilly, 1981, Sachis et al., 1982). In the cat, the afferent component in the cervical tract of the vagus nerve includes myelinated A- and B-fibers, and unmyelinated C-fibers, conveying sensory information from a number of organs, such as the heart, lungs,

The neurochemical consequences of vagus nerve stimulation

In the last decades the electrical stimulation of the vagus nerve has become the most widely used non-pharmacological treatment for refractory epilepsy (Treiman, 2010). More recently, VNS has been applied also to treat mood and cognitive disorders, from major depressive disorder to Alzheimer's disease (for a review, Beekwilder and Beems, 2010). One potential mechanism underlying the effects of VNS on seizures and mood is the alteration of norepinephrine (NE) release by projections of solitary

Ethical statement

Conflict of interest: None of the authors has actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations within three years of beginning the submitted work that could inappropriately influence, or be perceived to influence, their work.

Submission declaration: The present article has not been published previously and it is not under consideration for publication elsewhere, its publication is approved by all authors and

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