A Method of Nodose Ganglia Injection in Sprague-Dawley Rat

Afferent signaling via the vagus nerve transmits important general visceral information to the central nervous system from many diverse receptors located in the organs of the abdomen and thorax. The vagus nerve communicates information from stimuli such as heart rate, blood pressure, bronchopulmonary irritation, and gastrointestinal distension to the nucleus of solitary tract of the medulla. The cell bodies of the vagus nerve are located in the nodose and petrosal ganglia, of which the majority are located in the former. The nodose ganglia contain a wealth of receptors for amino acids, monoamines, neuropeptides, and other neurochemicals that can modify afferent vagus nerve activity. Modifying vagal afferents through systemic peripheral drug treatments targeted at the receptors on nodose ganglia has the potential of treating diseases such as sleep apnea, gastroesophageal reflux disease, or chronic cough. The protocol here describes a method of injection neurochemicals directly into the nodose ganglion. Injecting neurochemicals directly into the nodose ganglia allows study of effects solely on cell bodies that modulate afferent nerve activity, and prevents the complication of involving the central nervous system as seen in systemic neurochemical treatment. Using readily available and inexpensive equipment, intranodose ganglia injections are easily done in anesthetized Sprague-Dawley rats.     

Coexistence of neurons integrating urinary bladder activity and pelvic nerve activity in the same cardiovascular areas of the pontomedulla in cats

The present study examines the coexistence of neurons in the same cardiovascular point of the pontomedulla that integrates urinary bladder (UB) motility, and pelvic nerve activity (PNA). Microinjection of monosodium L-glutamate (Glu) into the locus coeruleus (LC), the gigantocellular tegmental field (FTG), the rostral ventrolateral medulla (RVLM), and the dorsomedial medulla (DM) produced pressor responses, whereas injection into the lateral tegmental field (FTL), the nucleus of tractus solitarii (NTS), and the caudal ventrolateral medulla (CVLM) produced depressor responses. However, microinjection of Glu into the dorsomotor nucleus of the vagus (DMV) and the ambiguus nucleus (AN), where the vagus nerve originates, produced marked bradycardia. Many of these cardiovascular responses were accompanied by increased, or decreased parasympathetic PNA. In six animals, sympathetic renal nerve activity (RNA) and PNA also increased simultaneously during the pressor response. The present study also examines the connection between the DMV-AN and the sacral intermediolateral column (IML), where parasympathetic preganglionic neurons (PGNs) of the pelvic nerve located. Biotinylated dextran amine (BDA), an anterograde tracer, was iontophoretically injected into the DMV or AN. No labelled terminal or neuron was detected in the sacral IML, but labelled terminals were observed in the bilateral LC, and also in the bilateral sides of the FTG, FTL, RVLM, DM, and CVLM. These results suggest that neurons of the DMV and/or AN may indirectly regulate the sacral parasympathetic PGNs through the LC for supraspinal control of the pelvic nerve. Furthermore, these results also suggest the coexistence of multiple autonomic integrating mechanisms of different kinds within various cardiovascular areas of the pontomedulla.     

Central pathways of pulmonary and lower airway vagal afferents.

Lung sensory receptors with afferent fibers coursing in the vagus nerves are broadly divided into three groups: slowly (SAR) and rapidly (RAR) adapting stretch receptors and bronchopulmonary C fibers. Central terminations of each group are found in largely nonoverlapping regions of the caudal half of the nucleus of the solitary tract (NTS). Second order neurons in the pathways from these receptors innervate neurons located in respiratory-related regions of the medulla, pons, and spinal cord. The relative ease of selective activation of SARs, and to a lesser extent RARs, has allowed for more complete physiological and morphological characterization of the second and higher order neurons in these pathways than for C fibers. A subset of NTS neurons receiving afferent input from SARs (termed pump or P-cells) mediates the Breuer-Hering reflex and inhibits neurons receiving afferent input from RARs. P-cells and second order neurons in the RAR pathway also provide inputs to regions of the ventrolateral medulla involved in control of respiratory motor pattern, i.e., regions containing a predominance of bulbospinal premotor neurons, as well as regions containing respiratory rhythm-generating neurons. Axon collaterals from both P-cells and RAR interneurons, and likely from NTS interneurons in the C-fiber pathway, project to the parabrachial pontine region where they may contribute to plasticity in respiratory control and integration of respiratory control with other systems, including those that provide for voluntary control of breathing, sleep-wake behavior, and emotions.     

Reinnervation of pulmonary stretch receptors

The Breuer-Hering reflex (BHR) reappears 12-14 wk after surgical lung denervation in beagle dogs (J. Appl. Physiol. 54: 1451-1456, 1983). To demonstrate that this is due to reinnervation of pulmonary stretch receptors, we recorded nerve activity from regenerated branches of the left vagus nerve in five beagle dogs. Ten days postdenervation the BHR was absent, whereas by 19 mo it was clearly present. Multifiber pulmonary afferent activity was observed in all five dogs with single-fiber activity observed in three. Sectioning the right vagus nerve did not alter the BHR, but sectioning all the regenerated branches of the left vagus abolished the reflex. In two additional dogs studied 17 mo postsurgery, recordings were made from few fiber nerve bundles of the left cervical vagus. Nerve activity was increased during gentle stroking of the surface of the left upper and lower lobes, indicating receptive fields in both lobes. These data demonstrate that reinnervation of pulmonary stretch receptors does occur and provides evidence that reinnervation of these receptors is responsible for return of the BHR after pulmonary denervation.     

Nodose ganglionectomy reduces angiotensin II receptor binding in the rat brainstem

Angiotensin II (Ang II) receptor binding sites in the dorsomedial medulla of intact and unilaterally nodose ganglionectomized rats were identified and characterized using 125I-sarcosine,isoleucine Ang II. This radioligand bound saturably and with high affinity to rat brain homogenates and to sections of rat brainstem. Specific (1 microM angiotensin II displaceable) binding of 125I-sarcosine,isoleucine Ang II was displaced by angiotensin analogues with a potency order similar to that described for angiotensin II receptors. Unilateral nodose ganglionectomy caused a reduction in Ang II receptor binding in the medial solitary tract nucleus, dorsal motor nucleus of the vagus, and area postrema ipsilateral to the lesioned ganglion. This observation suggests that Ang II receptors in the dorsomedial medulla may be located on axon terminals of vagal afferents and cell bodies of vagal efferents.     

Vanilloid receptor (VR1) expression in vagal afferent neurons innervating the gastrointestinal tract

The vanilloid receptor VR1 is a nonselective cation channel activated by capsaicin as well as increases in temperature and acidity, and can be viewed as molecular integrator of chemical and physical stimuli that elicit pain. The distribution of VR1 receptors in peripheral and central processes of rat primary vagal afferent neurons innervating the gastrointestinal tract was investigated by immunohistochemistry. Forty-two percent of neurons in the nodose ganglia retrogradely labeled from the stomach wall expressed low to moderate VR1 immunoreactivity (VR1-IR). VR1-IR was considerably lower in the nodose ganglia as compared to the jugular and dorsal root ganglia. In the vagus nerve, strongly VR1-IR fibers ran in separate fascicles that supplied mainly cervical and thoracic targets, leaving only weakly VR1-IR fibers in the subdiaphragmatic portion. Vagal afferent intraganglionic laminar endings (IGLEs) in the gastric and duodenal myenteric plexus did not express VR1-IR. Similarly, VR1-IR was contained in fibers running in perfect register with vagal afferents, but was not colocalized with horseradish peroxidase in the same varicosities of intramuscular arrays (IMAs) and vagal afferent fibers in the duodenal submucosa anterogradely labeled from the nodose ganglia. Only in the gastric mucosa did we find evidence for colocalization of VR1-IR in vagal afferent terminals. In contrast, many nerve fibers coursing through the myenteric and submucosal plexuses contained detectable VR1-IR, the majority of which colocalized calcitonin gene-related peptide immunoreactivity. In the dorsal medulla there was a dense plexus of VR1-IR varicose fibers in the commissural, dorsomedial and gelatinosus subnuclei of the medial NTS and the lateral aspects of the area postrema, which was substantially reduced, but not eliminated on the ipsilateral side after supranodose vagotomy. It is concluded that about half of the vagal afferents innervating the gastrointestinal tract express low levels of VR1-IR, but that presence in most of the peripheral terminal structures is below the immunohistochemical detection threshold.     

Electrical stimulation of afferent vagus nerve induces IL-1beta expression in the brain and activates HPA axis

Possible roles of the afferent vagus nerve in regulation of interleukin (IL)-1beta expression in the brain and hypothalamic-pituitary-adrenal (HPA) axis were examined in anesthetized rats. Levels of IL-1beta mRNA and protein in the brain were measured by comparative RT-PCR and ELISA. Direct electrical stimulation of the central end of the vagus nerve was performed continuously for 2 h. The afferent stimulation of the vagus nerve induced increases in the expression of mRNA and protein levels of IL-1beta in the hypothalamus and the hippocampus. Furthermore, expression of corticotropin-releasing factor mRNA was increased in the hypothalamus 2 h after vagal stimulation. Plasma levels of ACTH and corticosterone were also increased by this stimulation. The present results indicate that activation of the afferent vagus nerves itself can induce production of IL-1beta in the brain and activate the HPA axis. Therefore, the afferent vagus nerve may play an important role in transmitting peripheral signals to the brain in the infection and inflammation.     

Specific binding of the muscarinic antagonist [3H]quinuclidinyl benzilate is not associated with preganglionic motor neurons in the dorsal motor nucleus of the vagus

The present study evaluates the binding of [³H]quinuclidinyl benzilate, [³H]QNB, as a measure of cholinergic muscarinic binding in six areas of the rat medulla oblongata associated with the cranial nerves. In an experimental group, the right vagus nerve was severed in the neck in order to determine whether the specific muscarinic binding sites might be located on cells that contribute efferent fibers to the vagus nerve. The level of activity of choline acetyltransferase (ChAT) also was determined in the same six areas. Additional experiments utilizing the retrograde transport of toxic ricin, a 60,000 dalton agglutinin that acts as a potent ribosomal toxin, was carried out to further evaluate localization of specific muscarinic binding in the DMN after destruction of the preganglionic efferent cells. These results support the conclusion that specific binding of the muscarinic antagonist [³H]QNB observed in the DMN of the vagus of the rat is not associated with the large cells that contribute efferent fibers into the vagus nerve. We suggest that the specific cholinergic muscarinic binding is located on interneuronal cell surfaces, on afferent terminals of local circuit neurons, or on afferent terminals of long projection axons which arise from neurons in the brainstem, hypothalamus, or forebrain.This issue is dedicated to Donald B. Tower.     

Separation of hepatic and gastrointestinal signals from the common "hepatic" branch of the vagus

Anatomic studies show that the common hepatic branch (CHB) of the vagus contains afferent fibers that innervate sites outside the hepatoportal region, primarily in the gastrointestinal tract. In the current experiments on the anesthetized rat, the source of signals from the CHB was determined by recording CHB neurophysiological responses before and after transection of the gastroduodenal branch (GDB) of the CHB. Serotonin [5-hydroxytryptamine (5-HT)] and CCK-8 were used as probes to stimulate the CHB. Most of the CHB afferent fibers were 5-HT sensitive (56%), and 35% of these were also sensitive to CCK-8. Portal vein vs. jugular vein infusion of 5-HT and CCK-8 and GDB transection showed that 5-HT- and CCK-sensitive fibers innervate the hepatoportal region and areas outside the hepatic hilus (e.g., the gastrointestinal tract). Suppression of basal nerve activity by a 5-HT(3) receptor antagonist (Y-25130) suggests that approximately 50% of CHB afferent fibers contain 5-HT(3) receptors, but none of these fibers appears to be in the hepatoportal region because only in rats with an intact GDB did Y-25130 reduce nerve activity. In summary, these data are in close agreement with anatomic observations on the distribution of the CHB fibers and indicate that neurophysiological studies of the CHB must be carefully evaluated given the prominent role of nonhepatoportal afferent signals recorded from the CHB.     

Axonal Transport of Neuropeptides in the Cervical Vagus Nerve of the Rat

Accumulations of the neuropeptides substance P (SP), somatostatin (ST), and vasoactive intestinal polypeptide (VIP) proximal to a crush in the cervical vagus nerve of the rat have been measured using sensitive radioimmunoassays. Each of the peptides was rapidly transport towards the peripheral terminals of vagal afferent fibres, with average rates of flow ranging from 0.8 to 2.7 mm h-1. In the rabbit vagus nerve, SP was transported with an average rate of 4 mm h-1, which is more than double the rate for this peptide in the rat. Double crush experiments in rabbit vagus nerves indicated that the rapidly transported proportion of the total content of SP in the nerve free was about 34%. From this, the rate of transport of SP in the rapidly transported pool in the rabbit vagus nerve can be calculated to be 12 mm h-1 (280 mm day-1). Since such double crush experiments were not possible in the rat, it is not clear whether the different average rates of transport of SP in the rat and the rabbit reflect real differences in the rate of rapid transport in the two species. In common with rapid axonal transport of other neurotransmitters, the transport of SP and ST in the rat vagus nerve was blocked by colchicine, a drug that disrupts microtubules.     

Primary Vagal Projection to the Contralateral Non-NTS Region in the Embryonic Chick Brainstem Revealed by Optical Recording

Using multiple-site optical recording with the voltage-sensitive dye, NK2761, we found that vagus nerve stimulation in the embryonic chick brainstem elicits postsynaptic responses in an undefined region on the contralateral side. The characteristics of the contralateral optical signals suggested that they correspond to the monosynaptic response that is related to the vagal afferent fibers. The location of the contralateral response was different from the vagal motor nucleus (the dorsal motor nucleus of the vagus nerve) and sensory nucleus (the nucleus of the tractus solitarius), and other brainstem nuclei that receive primary vagal projection. These results show that the vagus nerve innervates and makes functional synaptic connections in a previously unreported region of the brainstem, and suggest that sensory information processing mediated by the vagus nerve is more complex than expected.     

Vagal innervation of guinea pig bronchial smooth muscle

We isolated the guinea pig right bronchus with the vagus nerves intact and evaluated the changes in isometric tension of the smooth muscle in response to nerve stimulation. Brief (10-s) trains of electrical field stimulation or vagus nerve stimulation caused a biphasic contraction: the "first phase" sensitive to atropine and the "second phase" sensitive to capsaicin. The two phases could be dissociated by adjusting the stimulus intensity; greater stimulus intensities (pulse durations or voltage) were required to evoke the capsaicin-sensitive phase. When stimulated at 30-min intervals, the magnitude of both phases of the contractions declined over a 2-h period of repeated stimulation; however, this was prevented by indomethacin. Stimulation of the left vagus nerve resulted in a monophasic contraction of the right bronchus, with little evidence of a capsaicin-sensitive phase. Blocking neurotransmission through the bronchial ganglion, as monitored by intracellular recording techniques, abolished the first-phase contraction but had no effect on the capsaicin-sensitive phase. Selective blockade of muscarinic M1 receptors had no effect on vagus nerve-mediated contractions. The results demonstrate that the left and right vagus nerves carry preganglionic fibers to the right bronchial ganglion. The right but not the left vagus nerve also carries capsaicin-sensitive afferent fibers that, when stimulated, result in a persistent contraction of the right bronchus. Finally, we provide functional and electrophysiological evidence supporting the hypothesis that capsaicin-sensitive afferent neurons communicate with postganglionic motoneurons within the bronchus.     

Mechanism of cardioventilatory coupling: insights from cardiac pacing, vagotomy, and sinoaortic denervation in the anesthetized rat

Cardioventilatory coupling (CVC), a temporal alignment between the heartbeat and inspiratory activity, is a major determinant of breath-to-breath variation in observed respiratory rate (f(o)). The cardiac-trigger hypothesis attributes this to adjustments of respiratory timing by baroreceptor afferent impulses to the central respiratory pattern generator. A mathematical model of this hypothesis indicates that apparent CVC in graphical plots of ECG R wave vs. inspiratory time is dependent on the heart rate (HR), the rate of the intrinsic respiratory oscillator (f(i)), and the strength of the hypothetical cardiovascular afferent impulse. Failure to account for HR and f(i) may explain the inconsistent results from previous attempts to identify the neural pathways involved in CVC. Cognizant of these interactions, we factored in the HR-to-f(i) ratio in our examination of the role of the vagus nerve and arterial baroreceptors in CVC by cardiac pacing 29 anesthetized Sprague-Dawley rats and incrementally changing the HR. With the assumption of a relatively constant f(i), CVC could be examined across a range of HR-to-f(o) ratios before and after vagotomy, sinoaortic denervation, and vagotomy + sinoaortic denervation. We confirmed the relation between CVC, HR-to-f(o) ratio, and breath-to-breath respiratory period variability and demonstrated the loss of these relations after baroreceptor elimination. Sham experiments (n = 8) showed that these changes were not due to surgical stress. Our data support the notion that inspiratory timing can be influenced by cardiac afferent activity. We conclude that the putative cardiovascular input arises from the arterial baroreceptors and that the vagus nerve is not critical for CVC.     

Morphological and physiological identification of medulla interneurons in the visual system of the tiger beetle larva

The morphology of visual interneurons in the tiger beetle larva was identified after recording their responses. Stained neurons were designated as either medulla or protocerebral neurons according to the location of their cell bodies. Medulla neurons were further subdivided into three groups. Afferent medulla neurons extended processes distally in the medulla neuropil and a single axon to the brain through the optic nerve. They received their main input from stemmata on the ipsilateral side. Two distance-sensitive neurons, near-by sensitive and far-sensitive neurons, were also identified. Atypical medulla neurons extended their neurites distally in the medulla and proximally to the brain, as afferent medulla neurons, but their input patterns and the shapes of their spikes differed from afferent neurons. Protocerebral neurons sent a single axon to the medulla neuropil. They spread collateral branches in the posterior region of the protocerebrum on its way to the medulla neuropil. They received main input from stemmata on the contralateral side. Medulla intrinsic neurons did not extend an axon to the brain, and received either bilateral or contralateral stemmata input only. The input patterns and discharge patterns of medulla neurons are discussed with reference to their morphology.     

顶核—延髓头端腹外侧区系统参与前庭降压降心率反应

实验用乌拉坦麻醉、箭毒化、人工呼吸的大鼠。将神经元胞体兴奋剂L-谷氨酸钠(Glu)微量注入顶核或前庭上核均引起血压下降;心率减慢。该顶核-和前庭上核-降压降心率反应均可被延髓头端腹外侧区内注射GABA受体阻断剂荷包牡丹碱阻断。顶核内注射普鲁卡因也能阻断Glu兴奋前庭上核的心血管反应。以上结果提示前庭-降压降心率反应可能通过顶核-延髓头端腹外侧区系统实现。静脉注射甲基阿托品也能衰减Glu兴奋顶核的心血管反应,显示迷走神经也参与前庭-顶核降压降心率反应。     

Trigeminal projections to contralateral dorsal horn: central extent, peripheral origins, and plasticity

Prior studies have documented a trigeminal (V) mandibular primary afferent projection to the dorsomedial portion of the contralateral medullary and cervical dorsal horns in cat, hamster, and rat. We now report the existence of a much more substantial V ophthalmic primary afferent projection to the ventrolateral portion of contralateral medullary and cervical dorsal horns in rat. Horseradish peroxidase (HRP) injections into the V ganglion or V brainstem complex anterogradely labeled a fascicle of primary afferent axons that exited the caudal ventrolateral V spinal tract to form a rostrocaudally continuous, transversely oriented, V primary afferent decussation. These fibers terminated most heavily in laminae III-V of the ventrolateral dorsal horn in contralateral caudal medulla and the first and second cervical segments. Retrograde tracing with diamidino yellow (DY) or fluorogold and anterograde tracing with Phaseolus vulgaris leucoagglutinin also demonstrated a substantial commissural projection of central origin in medullary dorsal horn laminae I-VII. The latter projection had a more diffuse trajectory and termination pattern than that of the V primary afferent decussation. Unilateral HRP injections into medullary and cervical dorsal horns also retrogradely labeled V primary afferent collaterals contralateral to the injection site in corresponding regions of dorsal horn, and also in ventromedial interpolaris, oralis, and principalis, rostral to their decussation. Axons (1.5 +/- 0.8 microns mean diameter; 0.4-3.9 microns range) therefore terminated both ipsi- and contralateral to their cells of origin. These HRP injections also labeled an average of 40.4 +/- 13.0 V ganglion cells (mean +/- SD, corrected for split somata) in dorsomedial, ophthalmic regions of the contralateral ganglion. Their mean diameter was slightly larger than that of cells labeled ipsilaterally (29.9 vs. 26.3 microns). Double-labeling studies assessed possible ophthalmic receptor surfaces innervated by centrally crossing primary afferents. DY was injected into right medullary and cervical dorsal horns, and HRP was applied to either the left cornea, the ethmoid nerve, or the dura overlying cerebral cortex. Though DY labeled from 75 to 125 left ganglion cells per animal, no cells were double-labeled. All of these findings suggest that nociceptive-specific ganglion cells are not a source of the crossed ophthalmic primary afferent projection. Unilateral transection of the infraorbital nerve on the day of birth did not alter the crossed primary afferent projection to the partially deafferented side of the brainstem. This is further evidence of an absence of central sprouting in spared V primary afferents following neonatal V deafferentation.     

Neuropeptide FF2 receptor distribution in the human brain. An immunohistochemical study

Human neuropeptide FF2 (hFF2) receptor has been postulated to mediate central autonomic regulation by virtue of its ability to bind with high affinity to many amidated neuropeptides. In the present immunohistochemical study, we identified hFF2 positive neurons in the forebrain and medulla oblongata of individuals, who died suddenly of mechanical trauma or hypothermia. Morphologically, these neurons demonstrated features identified with both projection neurons and interneurons. In the forebrain, the highest density of hFF2 expressing neurons was observed in the anterior amygdaloid area and dorsomedial hypothalamic nucleus, especially in its caudal part. A lesser density of hFF2 neurons was identified in the ventromedial hypothalamic nucleus, lateral and posterior hypothalamic areas whereas few cells were visualized in the paraventricular hypothalamic nucleus, perifornical nucleus, horizontal limb of the diagonal band, ventral division of the bed nucleus of the stria terminalis, nucleus basalis of Meynert and ventral tegmental area. In the medulla, significant numbers of hFF2 neurons were observed in the dorsal motor nucleus of vagus and to a lesser extent in the area of catecholaminergic cell groups, A1/C1. These data provide first immunohistochemical evidence of hFF2 localization in the human brain, which is consistent with that reported for tissue distribution of FF2 mRNA and FF2 binding sites within the brain of a variety of mammalian species. The distribution of hFF2 may help in identifying the role of amidated neuropeptides in the human brain within the context of central autonomic and neuroendocrine regulation.     

Function of nociceptin and opioid OP4 receptors in the regulation of the cardiovascular system.

Nociceptin is the endogenous ligand of the opioid OP4 or ORL1 (opioid receptor-like1) receptor. It decreases blood pressure and heart rate in anesthetized and conscious rats and mice after its intravenous and intracerebroventricular injection in a manner sensitive to OP4 but not to OP1-3 (or delta, kappa and mu opioid) receptor antagonists. OP4 receptors involved in the cardiovascular effects of nociceptin were identified on sensory afferent fibres, in brain areas including the nucleus tractus solitarii and the rostral ventrolateral medulla, on preganglionic and/or postganglionic sympathetic and parasympathetic nerve fibres innervating blood vessels and heart or directly on these target organs. These receptors do not seem to be tonically activated but may play a role in the pathophysiology of inflammation, arterial hypertension and cardiac or brain circulatory ischemia.     

Noradrenergic alpha 2 binding sites in vagal dorsal motor nucleus and nucleus tractus solitarius: autoradiographic localization

The distribution in the canine medulla oblongata of binding sites for p-[3H]aminoclonidine, a ligand specific for alpha 2-adrenergic receptors, was studied with light microscopic autoradiographic methods. Specific labelling was determined using unlabelled phentolamine as a displacer. The greatest density of sites was localized in the dorsal motor nucleus of the vagus nerve, the area postrema, and in several regions of the nucleus tractus solitarius. Less dense binding of the radioligand was also seen in the inferior olivary nucleus. Dorsomedial regions of the nucleus tractus solitarius were the most densely labelled in this nucleus, and dorsolateral and ventral regions were much less densely labelled. The region of the nucleus tractus solitarius shown in this study to be heavily labelled with alpha 2-adrenergic binding sites has been implicated in the autonomic control of blood pressure. The dorsal motor nucleus of the vagus, together with the nucleus tractus solitarius, may thus represent the site of the antihypertensive action of the drug clonidine, an alpha 2-adrenoreceptor agonist.     

The role of the vagus nerve in depression

The etiopathogenesis of depression is a highly complex process characterized by several neurobiological alterations including decreased monoamine neurotransmission in the brain, dysregulated hypothalamic-pituitary-adrenal axis activity, decreased neuronal plasticity, and chronic inflammation in the brain and peripheral tissues. Experimental and clinical studies indicate that the vagus nerve may influence these processes. The importance of the vagus nerve in the etiopathogenesis of depression is further supported by its involvement in the induction of sickness behavior, as well as by clinical studies confirming a beneficial effect of vagus nerve stimulation in depressed patients. The aim of this article is to describe current knowledge of afferent and efferent vagal pathways role in the development and progression of depression.