Induction of Fos-like protein in neurons of the medulla oblongata after electrical stimulation of the vagus nerve in anesthetized rabbit

doi:10.1016/0006-8993(94)91454-0

Brain Research

Volume 635, Issues 1–2, 28 January 1994, Pages 317-322

https://doi.org/10.1016/0006-8993(94)91454-0 Get rights and content

Abstract

Antibodies against the c-fos protein product Fos were used to map the first- and higher-order neurons in the rabbit medulla oblongata after electrical stimulation of the vagus nerve. Fos immunoreactivity appeared bilaterally except in the nucleus tractus solitarii. Seven areas were labeled: the nucleus tractus solitarii, the area postrema, the subnucleus lateralis caudalis magnocellularis medullar oblongata, the lateral reticular nucleus, the ambiguus nucleus, the dorsal part of the spinal trigeminal nucleus, the nucleus reticularis lateralis, the lateral border of the external cuneatus nucleus, the medial part of the inferior olivary nucleus (subnucleus β). The last two areas have never been visualized with conventional tracing techniques and may represent higher-order neurons connected to visceral vagal pathways. No labeling was observed in the nodose ganglion.

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Cited by (29)

Neuroendocrine homeostasis after vagus nerve stimulation in rats
2013, Psychoneuroendocrinology
Citation Excerpt :
Thus, the effect of VNS depends upon the state of the animal as well as stimulus intensity. Therefore, it is possible that anesthesia and high intensity VNS contributed toward the increases Fos-IR expression reported in the cNTS (Yousfi-Malki and Puizillout, 1994; Naritoku et al., 1995). Because the increases parallel seizure induced Fos-IR expression pattern (Kanter et al., 1996), a stress effect cannot be ruled out in these studies.
The vagus nerve is important in maintaining HPA axis and sympatho-adrenal system (SAS) homeostasis, however little is known about the effect of vagus nerve stimulation (VNS), as used therapeutically, on these functions. Accordingly, the effect of VNS on plasma indices of HPA axis (ACTH, corticosterone), and SAS (norepinephrine, epinephrine) function were evaluated in rats.
Male rats, on day-0 (D0), underwent surgeries for implantation of catheters into the right jugular vein and programmable (VNP) or non-programmable (VND) neurocybernetic devices encircling the left cervical vagus. On D7, after a blood sample, the device in VNP rats was programmed to deliver 500 μs width, 0.25 mA current pulses at 20 Hz (‘on’ 30 s, ‘off’ 5 min) followed by timed blood samples during the next 90 min. In acute studies, VNS was stopped at 60 min and the rats were perfused at 90 min to evaluate neuronal Fos immunoreactivity (Fos-IR). In chronic studies, the probe remained active. In these rats, the HPA axis response to airpuff-startle stressor (D17) and anterior pituitary CRF-receptor binding (D26) were evaluated.
During acute VNS, plasma indices of HPA axis and SAS activity, as well as Fos-IR activation pattern in brain regions known to increase after stress, were not different between VND and VNP rats. During chronic VNS, stress-induced HPA axis responses exhibited a tendency toward faster recovery to baseline in VNP rats.
Therapeutic VNS is not a stressor and does not compromise HPA axis or SAS homeostasis. Chronic VNS may facilitate development of efficient feedback mechanisms.
Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats
2011, Biological Psychiatry
Vagal nerve stimulation (VNS) is used for treatment-refractory depression, but there are few preclinical studies of its effects when administered repeatedly over time using clinically relevant stimulation parameters in nonanesthetized animals.
The novelty-suppressed feeding test (NSFT) and forced swim test (FST) were used to evaluate the anxiolytic- and antidepressant-like potential of VNS in rats, respectively. The behavioral effects of VNS were compared with those of desipramine (DMI; 10 mg/kg/day) and sertraline (7.5 mg/kg/day) administered via osmotic minipump. Such experiments were carried out in intact rats as well as those that had selective destruction of either serotonin or noradrenergic neurons in brain caused by the neurotoxins, 5,7-dihyroxytryptamine (5,7-DHT), or 6-hydroxydopamine (6-OHDA).
Repeated administration of VNS, DMI, and sertraline decreased latency to feed in the NSFT. In the FST, repeated VNS, DMI, and sertraline caused decreased immobility; the VNS-induced decrease in immobility resulted from increases in both swimming and climbing behaviors. Effects of VNS and sertraline, but not DMI, in both the NSFT and the FST were abolished in rats treated with 5,7-DHT. Effects of DMI in both behavioral tests, but not those of sertraline, were abolished in 6-OHDA treated rats. VNS effects on immobility and climbing in the FST were not blocked in the 6-OHDA-treated rats. There was no significant difference in locomotor activity caused by any of the treatments or by the lesions.
Serotonergic nerves are required for repeated VNS-induced anxiolytic- and antidepressant-like effects. Noradrenergic nerves can also be activated by VNS to cause its anxiolytic-like effect.
The Role Of Trigeminal Interpolaris-Caudalis Transition Zone In Persistent Orofacial Pain
2011, International Review of Neurobiology
Citation Excerpt :
The afferent projections to the ipsilateral dorsal Vi/Vc have been identified following HRP injection into the cervical vagus nerve (Gwyn et al., 1985). Electrical stimulation of the vagus nerve induces expression of Fos-LI in the Vi/Vc transition zone (Gieroba and Blessing, 1994; Yousfi-Malki and Puizillout, 1994). The vagotomy produces a decrease in the masseteric inflammation-induced Fos-LI in the Vi/Vc transition zone (Imbe et al., 1999).
Previous studies have established the role of the medullary dorsal horn or the subnucleus caudalis of the spinal trigeminal complex, a homolog of the dorsal horn of the spinal cord, in trigeminal pain processing. In addition to the medullary dorsal horn, recent studies have pointed out increased excitability and sensitization of trigeminal interpolaris and caudalis transition zone (Vi/Vc) following deep orofacial injury, involving neuron-glia-cytokine interactions. The Vi/Vc transition zone accesses rostral brain regions that are important for descending pain modulation, and somatovisceral and somatoautonomic processing and plays a unique role in coordinating trigeminal nocifensive responses.
Ablation of NK<inf>1</inf> receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats
2006, Brain Research
Citation Excerpt :
SP-SAP lesions that included both the subpostremal and the commissural NTS completely abolished the bradycardia and hypotension induced by activation of cardiopulmonary chemoreceptors with phenylbiguanide (Bezold-Jarisch reflex), indicating that NK1 receptor bearing neurons are essential for the cardiopulmonary chemoreflex. Both subpostremal and commissural NTS are known to be involved in the reflex, since stimulation of afferent fibers from cardiopulmonary receptors evokes neuronal activity in these areas (Hines et al., 1994; Kalia and Mesulam, 1980; Paton, 1998; Wilson et al., 1996a,b; Yousfi-Malki and Puizillout, 1994). This fits with our finding that lesions that were restricted to the subpostremal NTS reduced, but did not block the reflex.
The nucleus of the solitary tract (NTS) receives primary afferents involved in cardiovascular regulation. We investigated the role of NK₁-receptor bearing neurons in the NTS on cardiovascular reflexes in awake rats fitted with chronic venous and arterial cannulae. These neurons were lesioned selectively with saporin conjugated with substance P (SP-SAP, 2 μM, bilateral injections of 20 nL in the subpostremal NTS, or 200 nL in both the subpostremal and the commissural NTS). Before, and 7 and 14 days after injection of SP-SAP, we measured changes in blood pressure and heart rate induced by i.v. injection of phenylephrine and nitroprusside (baroreceptor reflex), cyanide (arterial chemoreceptor reflex), and phenylbiguanide (Bezold-Jarisch reflex). The smaller injections with SP-SAP completely abolished NK1 receptor staining in the subpostremal NTS. The larger injections abolished NK1 receptor immunoreactivity in an area that extended from the commissural NTS to the rostral end of the subpostremal NTS. The lesions seemed to affect only a limited number of neurons, since neutral red stained sections did not show any obvious reduction in cell number. The smaller lesions reduced the gain of baroreflex bradycardia and the hypotension induced by phenylbiguanide. The larger lesions completely abolished the response to phenylbiguanide, blocked the baroreflex bradycardia induced by phenylephrine, severely blunted the baroreflex tachycardia, and blocked the bradycardia and reduced the hypertension induced by cyanide. Thus, these responses depend critically on NK₁-receptor bearing neurons in the NTS.
Autonomic response and Fos expression in the NTS following intermittent vagal stimulation: Importance of pulse frequency
2006, Autonomic Neuroscience: Basic and Clinical
Chronic intermittent stimulation of the vagus nerve (VNS) is an approved adjunctive therapy of refractory epilepsy. Nevertheless, the circuits triggered by VNS under the variable conditions used in patients are not well understood. We analyzed the effect of increasing pulse frequency on physiological variables (intragastric pressure, cardiac and respiratory frequencies) and neuronal activation in the solitary tract nucleus (NTS), the entry level of peripheral vagal afferents, in the rat. For this purpose, we compared the subnuclear distribution of Fos-like immunoreactivity within the NTS following VNS at frequencies selected for their low (1 Hz) or high (10 Hz) therapeutic efficacy. In addition, NADPH diaphorase histochemistry was conducted in double-labeling experiments to check whether activated neurons may express nitric oxide (NO). We demonstrated that increasing pulse frequency had a major influence on the cardiorespiratory response to VNS and on the amount of activated neurons within NTS subdivisions engaged in cardiorespiratory control. These data, in line with clinical observations, suggested that within the range of therapeutic frequency, VNS may favor the regulation by vagal inputs of cortical activities within limbic areas involved in both epileptogenesis and cardiorespiratory afferent control. Furthermore, we did not find any evidence that anticonvulsant VNS might trigger NOergic neurons in the NTS.
Concurrent conditioned taste aversion: A learning mechanism based on rapid neural versus flexible humoral processing of visceral noxious substances
2005, Neuroscience and Biobehavioral Reviews
Taste aversion learning (TAL) consists of the avoidance of a taste previously associated with a noxious visceral stimulus. Clinical and experimental studies suggest that this adaptive process can be established by different procedures that imply distinct forms of learning and memory, although the final result is analogous, i.e. avoidance of the gustatory stimulus associated with gastrointestinal discomfort. In fact, a double neurobiological system has been anatomically dissociated and, functionally, may be implicated in nausea and emesis, in food selection, and in neuroimmune interactions. Actually, a dual, parallel, and non-redundant gut–brain system has been proposed that sustain two different TAL modalities, concurrent and sequential. Concurrent TAL requires several trials and is inflexible, requiring simultaneity of the stimuli and the participation of the vagus nerve. In contrast, sequential TAL can be acquired in one trial and is flexible, permits long inter-stimulus delays, and is independent of vagal pathways. These two TAL modalities are analyzed in the light of the recent proposal that different acquisition processes are sustained by distinct cerebral systems.

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Abstract

Reference (29)

C-fos expression in rat lumbar spinal cord following peripheral stimulation in adjuvant-induced arthritic and normal rats

Brain Res.

Effects of morphine and naloxone on basal and evoked Fos-like immunoreactivity in lumbar spinal cord neurons of arthritic rats

Pain

Peripheral bombesin induces c-fos protein in the rat brain

Brain Res.

The induction and suppression of c-fos expression in the rat brain by cholecystokinin and its antagonist L364, 718

Neurosci. Lett.

Projections from the inferior olive to the cerebellar nuclei in the cat demonstrated by retrograde transport of horseradish peroxidase

Brain Res.

Induction of c-fos mRNA and protein in neurons and glia after traumatic brain injury: pharmacological characterization

Brain Res.

Fos-like protein is induced in neurons of the medulla oblongata after stimulation of the carotid sinus nerve in awake and anesthetized rats

Brain Res.

Transneuronal labelling of neurons in rabbit brain after injection or Herpes simplex virus type 1 into the aortic depressor nerve

Brain Res.

Viruses as transneuronal tracers

Trends Neurosci.

Expression of c-fos protein in rat brain after electrical stimulation of the aortic depressor nerve

Brain Res.

Golgi-like, transneuronal retrograde labelling with CNS injections of Herpes simplex virus type 1

Brain Res. Bull.

The regulation and function of c-Fos and other immediate early genes in the nervous system

Neuron

Opiates modify induction of c-fos proto-oncogene in the spinal cord of the rat following noxious stimulation

Neurosci. Lett.

Changes in the visual system of monocularly saturated or enucleated cats demonstrable with cytochrome oxidase histochemistry

Brain Res.

Cited by (29)

Neuroendocrine homeostasis after vagus nerve stimulation in rats

Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats

The Role Of Trigeminal Interpolaris-Caudalis Transition Zone In Persistent Orofacial Pain

Ablation of NK<inf>1</inf> receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats

Autonomic response and Fos expression in the NTS following intermittent vagal stimulation: Importance of pulse frequency

Concurrent conditioned taste aversion: A learning mechanism based on rapid neural versus flexible humoral processing of visceral noxious substances