Efferent projections of the nucleus of the solitary tract to peri-locus coeruleus dendrites in rat brain: Evidence for a monosynaptic pathway

Bockstaele, Elisabeth J. Van; Peoples, James; Telegan, Patti

doi:10.1002/(sici)1096-9861(19990927)412:3<410::aid-cne3>3.0.co;2-f

Cited by 201 publications

(158 citation statements)

References 105 publications

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“…The locus coeruleus (LC) is the major NE brainstem nucleus that sends projections to many brain areas, including limbic structures. It receives innervation from the nucleus of the solitary tract (Van Bockstaele et al, 1999), a brainstem nucleus for vagus nerve afferents (Barraco, 1994). In addition, the DRN innervates the LC (Cedarbaum and Aghajanian, 1978;Leger and Descarries, 1978), and, conversely, the LC gives NE inputs to the DRN (Baraban and Aghajanian, 1980), creating ample opportunity for cross-modulation.…”

mentioning

confidence: 74%

Effect of Vagus Nerve Stimulation on Serotonergic and Noradrenergic Transmission

Dorr

Debonnel²

2006

J Pharmacol Exp Ther

345

242

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Vagus nerve stimulation (VNS) is an antiepileptic treatment, which has recently shown promise as an antidepressant. Yet, its antidepressant mechanisms of action are unknown. Serotonergic [5-hydroxytryptamine (5-HT, serotonin)] and noradrenergic [norepinephrine (NE)] systems are involved in the pathophysiology of depression and in the mechanisms of action of antidepressants. The present study analyzes 5-HT and NE neuronal firing rates in their brainstem nuclei: the dorsal raphe nucleus (DRN) and locus coeruleus (LC), respectively. The basal firing rates in the DRN and LC were significantly increased after long-term treatments with VNS. After short-term VNS treatments, firing rates were significantly higher for LC (at 1 h and 3 days). As changes in their firing rate may have been due to altered autoreceptor sensitivities, the responses of autoreceptors to the acute administration of their respective agonists were assessed. However, no significant difference was seen in the DRN. No significant differences in dose response curves for 5-HT 1A somatodendritic and ␣ 2 -adrenergic autoreceptors were noticed between long-term VNS and controls. VNS appears to have a novel mechanism of antidepressant action, enabling its effectiveness in treatment-resistant depression. LC firing rates significantly increase earlier than the DRN basal firing. As the LC has an excitatory influence on DRN, it is possible that the increased DRN firing rate is secondary to an initial increased LC firing rate from VNS.The vagus nerve (cranial nerve 10) is generally thought of as a group of efferent parasympathetic fibers regulating autonomic functions. However, this nerve consists of 80% afferent fibers (Foley and DuBois, 1937) from the head, neck, and body, leading up toward the cerebrum. These afferent fibers were targeted for therapeutic use by stimulation in medically and surgically intractable epilepsy, with several patients reporting a large decrease in seizure frequency (reviewed in .In addition to decreasing seizure frequency, an improvement in mood was witnessed in patients with vagus nerve stimulation (VNS), even in those with little or no change in seizure frequency (Harden et al., 2000). Clinical studies with VNS in treatment-resistant depression have generated positive results, with 3-month treatments inducing a 31% response rate and a 15% remission rate, based on Hamilton Rating Scales for Depression scores. Response and remission rates increased further with longer VNS treatments (Nahas et al., 2005). Recently, Krahl et al. (2004) showed that VNS significantly reduced immobility in rats with the forced-swim test, an animal model used to predict antidepressant treatments efficacy. The immobility levels of VNS-treated animals were similar to those of animals treated with desipramine and electroconvulsive therapy (ECT), two antidepressant treatments. VNS therapy is now approved for treatment-resistant depression in the European Union, the United States, and Canada, but its mechanisms of action in depression are unknown.

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mentioning

confidence: 74%

Effect of Vagus Nerve Stimulation on Serotonergic and Noradrenergic Transmission

Dorr

Debonnel²

2006

J Pharmacol Exp Ther

345

242

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“…This hypothesis is supported by several lines of converging evidence in the literature. First, the vagus nerve afferent fibers project to the nucleus of the solitary tract; in turn, the nucleus of the solitary tract projects both directly and indirectly to the LC [44]. Acute electrical stimulation of the vagus nerve induces an increase in the discharge rate of LC noradrenergic neurons [45].…”

Section: Discussionmentioning

confidence: 99%

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

et al. 2014

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Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient's response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (≤50 %). Two stimulation conditions were compared: VNS OFF and VNS ON. In each condition, the P3 component was measured during an auditory oddball paradigm. VNS induced a significant increase of the P3 amplitude at the parietal midline electrode, in VNS responders only. In addition, logistic regression analysis showed that the increase of P3 amplitude can be used as a noninvasive indicator for VNS responders. These results support the hypothesis that activation of the locus coeruleus noradrenergic system is associated with the antiepileptic effect of VNS. Modulation of the P3 amplitude should be further investigated as a noninvasive biomarker for the therapeutic efficacy of VNS in patients with refractory epilepsy.

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“…The NTS also projects both directly and indirectly to the LC (Van Bockstaele et al, 1999). Indeed, several lines of evidence support the hypothesis that VNS activates neurons in the LC.…”

Section: Vagus Nerve -Locus Coeruleus Connectionmentioning

confidence: 99%

Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat

Roosevelt¹,

et al. 2006

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The vagus nerve is an important source of afferent information about visceral states and it provides input to the locus coeruleus (LC), the major source of norepinephrine (NE) in the brain. It has been suggested that the effects of electrical stimulation of the vagus nerve on learning and memory, mood, seizure suppression, and recovery of function following brain damage are mediated, in part, by the release of brain NE. The hypothesis that left vagus nerve stimulation (VNS) at the cervical level results in increased extracellular NE concentrations in the cortex and hippocampus was tested at four stimulus intensities 0.0, 0.25, 0.5, and 1.0 mA. Stimulation at 0.0 and 0.25 mA had no effect on NE concentrations, while the 0.5 mA stimulation increased NE concentrations significantly in the hippocampus (23%), but not the cortex. However, 1.0 mA stimulation significantly increased NE concentrations in both the cortex (39%) and hippocampus (28%) bilaterally. The increases in NE were transient and confined to the stimulation periods. VNS did not alter NE concentrations in either structure during the inter-stimulation baseline periods. No differences were observed between NE levels in the initial baseline and the post-stimulation baselines. These findings support the hypothesis that VNS increases extracellular NE concentrations in both the hippocampus and cortex.

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Efferent projections of the nucleus of the solitary tract to peri-locus coeruleus dendrites in rat brain: Evidence for a monosynaptic pathway

Cited by 201 publications

References 105 publications

Effect of Vagus Nerve Stimulation on Serotonergic and Noradrenergic Transmission

Effect of Vagus Nerve Stimulation on Serotonergic and Noradrenergic Transmission

The P3 Event-Related Potential is a Biomarker for the Efficacy of Vagus Nerve Stimulation in Patients with Epilepsy

Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat

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