title: Autonomic response and Fos expression in the NTS following intermittent vagal stimulation: importance of pulse frequency.
abstract: 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.
authors.affiliation: GERM, CNRS FRE 2722, 280, bd de Sainte-Marguerite, 13009 Marseille, France.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Osharina
authors.forename: Vitaly
authors.initials: V
authors.lastname: Bagaev
authors.forename: Fabrice
authors.initials: F
authors.lastname: Wallois
authors.forename: Nicole
authors.initials: N
authors.lastname: Larnicol
mesh_terms: D000818:Animals; D002452:Cell Count / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D007839:Functional Laterality / Q000502:physiology; D015870:Gene Expression / Q000502:physiology* / Q000528:radiation effects; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D014630:Vagus Nerve / Q000502:physiology* / Q000528:radiation effects
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D009569:Nitric Oxide; D009252:NADPH Dehydrogenase