Rinaman L. Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure. Brain Res 1350: 18-34

Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Brain research (Impact Factor: 2.84). 03/2010; 1350:18-34. DOI: 10.1016/j.brainres.2010.03.059
Source: PubMed


Metabolic homeostasis reflects the complex output of endocrine, autonomic, and behavioral control circuits that extend throughout the central nervous system. Brain regions that control food intake and energy expenditure are privy to continuous visceral sensory feedback signals that presumably modulate appetite, satiety, digestion, and metabolism. Sensory signals from the gastrointestinal tract and associated digestive viscera are delivered to the brain primarily by vagal afferents that terminate centrally within the caudal nucleus of the solitary tract (NST), with signals subsequently relayed to higher brain regions by parallel noradrenergic and peptidergic projection pathways arising within the NST. This article begins with an overview of these ascending pathways identified in adult rats using a standard anterograde tracer microinjected into the caudal visceral sensory region of the NST, and also by immunocytochemical localization of glucagon-like peptide-1. NST projection targets identified by these two approaches are compared to the distribution of neurons that become infected after inoculating the ventral stomach wall with a neurotropic virus that transneuronally infects synaptically-linked chains of neurons in the anterograde (i.e., ascending sensory) direction. Although the focus of this article is the anatomical organization of axonal projections from the caudal visceral NST to the hypothalamus and limbic forebrain, discussion is included regarding the hypothesized role of these projections in modulating behavioral arousal and coordinating endocrine and behavioral (i.e., hypophagic) responses to stress.

  • Source
    • "In particular, activation of the nucleus tractus solitarii (NTS) may be crucial for the central effects of peripherally released PP. The NTS is important for sensing glucose levels and it responds to hypoglycemia by stimulating food intake, inducing release of stress hormones and increasing sympathetic tone (Renner et al., 2010; Rinaman, 2010; Wu et al., 2012). Interestingly, extinction-promoting effects are known for glucocorticoids and yohimbine, both compounds that increase stress and sympathetic activity (Barrett and Gonzalez-Lima, 2004; Yang et al., 2006; Holmes and Quirk, 2010; Blundell et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: Avoiding danger and finding food are closely related behaviours that are essential for surviving in a natural environment. Growing evidence supports an important role of gut-brain peptides in modulating energy homeostasis and emotional-affective behaviour. For instance, postprandial released pancreatic polypeptide (PP) reduces food intake and alters stress-induced motor activity and anxiety by activating central Y4 receptors. Experimental approach: We used Y4KO mice and peripheral injections of the long-acting Y4 receptor agonist [K(30) (PEG2)]hPP2-36 to investigate the role of Y4 receptors in Pavlovian fear conditioning. Extinction and relapse after extinction was measured by spontaneous recovery and renewal tests. Key results: We demonstrate that in mice deletion of Y4 receptors impairs cued and context fear extinction without affecting acquisition, consolidation or recall of fear. Correspondingly, peripheral injection of [K(30) (PEG2)]hPP2-36 facilitated extinction learning upon fasting, an effect that was long-lasting and generalized. Furthermore, peripherally applied [K(30) (PEG2)]hPP2-36 before extinction inhibited the activation of orexin-expressing neurons in the lateral hypothalamus in WT, but not in Y4KO mice. This suggests suppression of excessive arousal as a possible mechanism for the extinction-promoting effect of central Y4 receptors. Conclusions and implications: Our findings provide strong evidence that fear extinction requires the integration of vegetative stimuli with cortical and subcortical information, a process crucially depending on Y4 receptors. Importantly, in the lateral hypothalamus two peptide systems, PP and orexin, interact to generate an emotional response adapted to the current homeostatic state. A detailed investigation of feeding-relevant genes may thus deliver multiple intervention points for treating anxiety-related disorders. This article is protected by copyright. All rights reserved.
    Full-text · Article · Feb 2016 · British Journal of Pharmacology
  • Source
    • "Control of food intake in the brain is regulated by the integration of both the neuronal and humoral signals from the periphery. A variety of sensory information derived from the gastrointestinal tract is transmitted to the nucleus of the tractus solitaries (NTS) in the medulla oblongata via the vagal afferent nerve, terminating in hypothalamic nuclei implicated in the control of feeding (Rinaman 2010). The nodose ganglion, located outside the jugular foramen, is a constellation of vagal afferent neurons that synthesize receptors for gut peptides that regulate feeding and energy homeostasis (Zhuo et al. 1997, Konturek et al. 2004). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ghrelin, a stomach-derived orexigenic peptide, transmits starvation signals to the hypothalamus via the vagus afferent nerve. Peripheral administration of ghrelin does not induce food intake in high fat diet (HFD)-induced obese mice. We investigated whether this ghrelin resistance was caused by dysfunction of the vagus afferent pathway. Subcutaneous ghrelin administration did not induce food intake, suppression of oxygen consumption, electrical activity of the vagal afferent nerve, phosphorylation of extracellular-signal-regulated kinases 2 (ERK2) and AMP-activated protein kinase α (AMPKα) in the nodose ganglion, or Fos expression in hypothalamic arcuate nucleus of mice fed a HFD for 12 weeks. Administration of anti-ghrelin IgG did not induce suppression of food intake in HFD-fed mice. Expression levels of ghrelin receptor mRNA in the nodose ganglion and hypothalamus of HFD-fed mice were reduced. Inflammatory responses, including upregulation of macrophage/microglia markers and inflammatory cytokines, occurred in the nodose ganglion and hypothalamus of HFD-fed mice. A high-fat diet blunted ghrelin signaling in the nodose ganglion via a mechanism involving in situ activation of inflammation. These results show that ghrelin resistance in the obese state may be caused by dysregulation of ghrelin signaling via the vagal afferent.
    Full-text · Article · May 2015 · Journal of Endocrinology
  • Source
    • "Recently , it has been demonstrated that DMV is a part of the dorsal motor complex, composed the nucleus tractus solitarii (NTS) and area postrema (Wang et al. 2014). NTS projects to many brain areas including the hindbrain, midbrain and forebrain, and dopamine-related brain structures—the ventral tegmental area (VTA) and nucleus accumbens (NAC) (Merchenthaler et al. 1999; Rinaman 2010). In addition, the vagus nerve connects the DMV with, among others, the gastrointestinal system, which is considered to be significantly affected at the onset of PD, even before motor signs occur (Braak et al. 2003). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the co-occurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders.
    Full-text · Article · Apr 2015 · NeuroMolecular Medicine
Show more