Central control of gastrointestinal motility

Kirsteen N Browning, R Alberto Travagli, Kirsteen N Browning, R Alberto Travagli

Abstract

Purpose of review: This review summarizes the organization and structure of vagal neurocircuits controlling the upper gastrointestinal tract, and more recent studies investigating their role in the regulation of gastric motility under physiological, as well as pathophysiological, conditions.

Recent findings: Vagal neurocircuits regulating gastric functions are highly plastic, and open to modulation by a variety of inputs, both peripheral and central. Recent research in the fields of obesity, development, stress, and neurological disorders highlight the importance of central inputs onto these brainstem neurocircuits in the regulation of gastric motility.

Summary: Recognition of the pivotal role that the central nervous system exerts in the regulation, integration, and modulation of gastric motility should serve to encourage research into central mechanisms regulating peripheral motility disorders.

Conflict of interest statement

Conflicts of interest

There are no conflicts of interest.

References

    1. Langley JN. The autonomic nervous system, part 1. Cambridge: W. Heffer & Sons Ltd; 1921.
    1. Furness JB. The enteric nervous system and neurogastroenterology. Nat Rev Gastroenterol Hepatol 2012; 9:286–294.
    1. Fox EA, Powley TL. Longitudinal columnarorganization withinthedorsal motor nucleus represents separate branches of the abdominal vagus. Brain Res 1985; 341:269–282.
    1. Norgren R, Smith GP. Central distribution of subdiaphragmatic vagal branches in the rat. J Comp Neurol 1988; 273:207–223.
    1. Shapiro RE, Miselis RR. The central organization ofthe vagus nerve innervating the stomach ofthe rat. J Comp Neurol 1985; 238:473–488.
    1. Browning KN, Renehan WE, Travagli RA. Electrophysiological and morphological heterogeneity of rat dorsal vagal neurones which project to specific areas of the gastrointestinal tract. J Physiol 1999; 517:521–532.
    1. Travagli RA, Gillis RA. Hyperpolarization-activated currents IH and IKIR in rat dorsal motor nucleus of the vagus neurons, in vitro. J Neurophysiol 1994; 71:1308–1317.
    1. Travagli RA, Gillis RA, Rossiter CD, Vicini S. Glutamate and GABA-mediated synaptic currents in neurons ofthe ratdorsal motor nucleus ofthevagus. AmJ Physiol 1991; 260:G531–G536.
    1. Sivarao DV, Krowicki ZK, Hornby PJ. Role of GABAA receptors in rat hindbrain nuclei controlling gastric motor function. Neurogastroenterol Motil 1998; 10:305–313.
    1. Davis SF, Derbenev AV, Williams KW, et al. Excitatory and inhibitory local circuit input to the rat dorsal motor nucleus of the vagus originating from the nucleus tractus solitarius. Brain Res 2004; 1017:208–217.
    1. Babic T, Browning KN, Travagli RA. Differential organization of excitatory and inhibitory synapses within the rat dorsal vagal complex. Am J Physiol Gastro-intest Liver Physiol 2011; 300:G21–G32.
    1. Altschuler SM, Bao X, Bieger D, et al. Viscerotopic representation of the upper alimentarytract in the rat: sensory ganglia and nuclei ofthe solitary and spinal trigeminal tracts. J Comp Neurol 1989; 283:248–268.
    1. Broussard DL, Altschuler SM. Brainstem viscerotopic organization of afferents and efferents involved in the control of swallowing. Am J Med 2000; 108:79S–86S.
    1. Raybould HE. Does your guttaste? Sensory transduction in the gastrointestinal tract. News Physiol Sci 1998; 13:275–280.
    1. Raybould HE. Visceral perception: sensory transduction in visceral afferents and nutrients. Gut 2002; 51(Suppl 1):I11–I14.
    1. Dockray G Gutendocrine secretions and their relevancetosatiety. CurrOpin Pharmacol 2004; 4:557–560.
    1. Browning KN, Travagli RA. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr Physiol 2014; 4:1339–1368.
    1. Cottrell GT, Ferguson AV. Sensory circumventricular organs: central roles in integrated autonomic regulation. Regul Pept 2004; 117:11–23.
    1. Fry M, Ferguson AV. The sensory circumventricular organs: brain targets for circulating signals controlling ingestive behavior. Physiol Behav 2007; 91:413–423.
    1. Baptista V, Browning KN, Travagli RA. Effects of cholecystokinin-8s in the nucleus tractus solitarius of vagally deafferented rats. Am J Physiol Regul Integr Comp Physiol 2007; 292:R1092–R1100.
    1. Trapp S, Richards JE. The gut hormone glucagon-like peptide-1 produced in brain: is this physiologically relevant? Curr Opin Pharmacol 2013; 13: 964–969.
    1. Card JP, Johnson AL, Llewellyn-Smith IJ, et al. Glp-1 neurons form a local synaptic circuit within the rodent nucleus ofthe solitary tract. J Comp Neurol 2018; 526:2149–2164.
    1. Browning KN, Travagli RA. Plasticity of vagal brainstem circuits in the control of gastrointestinal function. Auton Neurosci 2011; 161:6–13.
    1. Browning KN, Travagli RA. Plasticity of vagal brainstem circuits in the control of gastric function. Neurogastroenterol Motil 2010; 22:1154–1163.
    1. Rinaman L, Card JP, Schwaber JS, Miselis RR. Ultrastructural demonstration ofagastric monsynaptic vagal circuit in the nucleus ofthe solitarytract in rat. J Neurosci 1989; 9:1985–1996.
    1. Browning KN, Travagli RA. The peptide TRH uncovers the presence of presynaptic 5-HT1A receptors via activation of a second messenger pathway in the rat dorsal vagal complex. J Physiol 2001; 531:425–435.
    1. Browning KN, Kalyuzhny AE, Travagli RA. Mu-opioid receptor trafficking on inhibitory synapses in the rat brainstem. J Neurosci 2004; 24:7344–7352.
    1. Browning KN, Kalyuzhny AE, Travagli RA. Opioid peptides inhibit excitatory but not inhibitory synaptic transmission in the rat dorsal motor nucleus ofthe vagus. J Neurosci 2002; 22:2998–3004.
    1. Browning KN, Travagli RA. Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by camp levels. Neurogastroenterol Motil 2009; 21:1309–1318.
    1. Browning KN, Babic T, Toti L, et al. Plasticity in the brainstem vagal circuits controlling gastric motorfunction triggered by corticotropin releasing factor. J Physiol 2014; 592:4591–4605.
    1. Blake CB, Smith BN. Camp-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice. Am J Physiol Regul Integr Comp Physiol 2014; 307:R711–R720.
    1. Browning KN, Travagli RA. Functional organization of presynaptic metabotropic glutamate receptors in vagal brainstem circuits. J Neurosci 2007; 27:8979–8988.
    1. Kentish SJ, Frisby CL, Kennaway DJ, et al. Circadian variation in gastric vagal afferent mechanosensitivity. J Neurosci 2013; 33:19238–19242.
    1. Kentish SJ,Vincent AD, Kennaway DJ, et al. High-fatdiet-induced obesity ablates gastric vagal afferent circadian rhythms. J Neurosci 2016; 36:3199–3207.This manuscript defines the circadian rhythmicity of gastric mechanosensitive vagal afferents, which renders vagal mechanosensors less sensitive to gastric stretch and distention during the dark period, allowing increased food intake at a time of higher energy demand. HFD ablates this normal diurnal rhythm, decreasing mechanosensitivity during the light period, increasing food intake, and contributing to the development of obesity.
    1. Kentish SJ, Hatzinikolas G, Li H, et al. Time-restricted feeding prevents ablation ofdiurnal rhythms in gastric vagal afferent mechanosensitivity observed in high-fat diet-induced obese mice. J Neurosci 2018; 38:5088–5095.This manuscript describes the effects of time-restricted feeding to prevent the actions of HFD to ablate diurnal rhythmicity in gastric mechanosensitive vagal afferents, implying that vagal afferent function can be modulated by both nutrient content as well as timing of food intake.
    1. Berthoud HR. Homeostatic and nonhomeostatic pathways involved in the control of food intake and energy balance. Obesity (Silver Spring) 2006; 14(Suppl 5):197S–200S.
    1. Berthoud HR, Morrison C. The brain, appetite, and obesity. Annu Rev Psychol 2008; 59:55–92.
    1. Schwartz MW, Woods SC, Porte D, et al. Central nervous system control of food intake. Nature 2000; 404:661–671.
    1. Bhagat R, Fortna SR, Browning KN. Exposure to a high fat diet during the perinatal period alters vagal motoneurone excitability, even in the absence of obesity. J Physiol 2015; 593:285–303.
    1. Browning KN, Fortna SR, Hajnal A. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones. J Physiol 2013; 591:2357–2372.
    1. Camilleri M Peripheral mechanisms in appetite regulation. Gastroenterology 2015; 148:1219–1233.
    1. Feinle-Bisset C Upper gastrointestinal sensitivity to meal-related signals in adult humans: relevance to appetite regulation and gut symptoms in health, obesity and functional dyspepsia. Physiol Behav 2016; 162:69–82.
    1. Janssen P, Vanden Berghe P, Verschueren S, et al. Review article: the role of gastric motility in the control of food intake. Aliment Pharmacol Ther 2011; 33:880–894.
    1. Clyburn C, Travagli RA, Browning KN. Acute high-fat diet upregulates glutamatergic signaling in the dorsal motor nucleus ofthe vagus. Am J Physiol Gastrointest Liver Physiol 2018; 314:G623–G634.This study describes diet-induced short-term plasticity in central vagal neurocircuits that regulates vagal efferent control of gastric functions and may be of importance in the homeostatic regulation of food intake and caloric consumption.
    1. Rinaman L Postnatal development of central feeding circuits In: Stricker E, Woods S, editors. Neurobiology of food and fluid intake, vol. 14 New York: Plenum Publishers; 2004. pp. 159–194.
    1. Rinaman L Postnatal development of hypothalamic inputs to the dorsal vagal complex in rats. Physiol Behav 2003; 79:65–70.
    1. Rinaman L, Levitt P. Establishment of vagal sensorimotor circuits during fetal development in rats. J Neurobiol 1993; 24:641–659.
    1. Rinaman L, Banihashemi L, Koehnle TJ. Early life experience shapes the functional organization of stress-responsive visceral circuits. Physiol Behav 2011; 104:632–640.
    1. Greenwood-Van Meerveld B, Johnson AC. Stress-induced chronic visceral pain of gastrointestinal origin. Front Syst Neurosci 2017; 11:86.
    1. Banihashemi L, Rinaman L. Repeated brief postnatal maternal separation enhances hypothalamic gastric autonomic circuits in juvenile rats. Neuroscience 2010; 165:265–277.
    1. Card JP, Levitt P, Gluhovsky M, Rinaman L. Early experience modifies the postnatal assembly of autonomic emotional motor circuits in rats. J Neurosci 2005; 25:9102–9111.
    1. Sasaki A, de Vega WC, St-Cyr S, et al. Perinatal high fat diet alters glucocorticoid signaling and anxiety behavior in adulthood. Neuroscience 2013; 240:1–12.
    1. McMenamin CA, Travagli RA, Browning KN. Perinatal high fat diet increases inhibition of dorsal motor nucleus of the vagus neurons regulating gastric functions. Neurogastroenterol Motil 2017; 30:. doi: 10.1111/nmo.13150.
    1. Sullivan EL, Smith MS, Grove KL. Perinatal exposure to high-fatdiet programs energy balance, metabolism and behavior in adulthood. Neuroendocrinology 2011; 93:1–8.
    1. Babygirija R, Zheng J, Ludwig K, Takahashi T. Central oxytocin is involved in restoring impaired gastric motility following chronic repeated stress in mice. Am J Physiol Regul Integr Comp Physiol 2010; 298:R157–R165.
    1. Bulbul M, Babygirija R, Ludwig K, Takahashi T. Central oxytocin attenuates augmented gastric postprandial motility induced by restraint stress in rats. Neurosci Lett 2010; 479:302–306.
    1. Nakade Y, Tsuchida D, Fukuda H, et al. Restraint stress delays solid gastric emptying via a central corticotropin-releasing factor and peripheral sympathetic neuron in rats. Am J Physiol Regul Integr Comp Physiol 2005; 288:R427–R432.
    1. Tsukamoto K, Nakade Y, Mantyh C, et al. Peripherally administered CRF stimulates colonic motility via central CRF receptors and vagal pathways in conscious rats. Am J Physiol Regul Integr Comp Physiol 2006; 290:R1537–R1541.
    1. Zheng J, Dobner A, Babygirija R, et al. Effects of repeated restraint stress on gastric motility in rats. Am J Physiol Regul Integr Comp Physiol 2009; 296:R1358–R1365.
    1. Stengel A, Tache Y. Neuroendocrine control of the gut during stress: corticotropin-releasing factor signaling pathways in the spotlight. Annu Rev Physiol 2009; 71:219–239.
    1. Tache Y, Bonaz B. Corticotropin-releasing factor receptors and stress-related alterations of gut motor function. J Clin Invest 2007; 117:33–40.
    1. Khoo J, Rayner CK, Feinle-Bisset C, et al. Gastrointestinal hormonal dysfunction in gastroparesis and functional dyspepsia. Neurogastroenterol Motil 2010; 22:1270–1278.
    1. Czimmer J, Tache Y. Peripheral corticotropin releasing factorsignaling inhibits gastric emptying: mechanisms of action and role in stress-related gastric alterations of motor function. Curr Pharm Des 2017; 23:4042–4047.
    1. Babygirija R, Bulbul M, Yoshimoto S, et al. Central and peripheral release of oxytocin following chronic homotypic stress in rats. Auton Neurosci 2012; 167:56–60.
    1. Jiang Y, Browning KN, Toti L, Travagli RA. Vagally mediated gastric effects of brain stem α2 -adrenoceptor activation in stressed rats. Am J Physiol Gastrointest Liver Physiol 2018; 314:G504–G516.
    1. Jiang Y, Holly Coleman F, Kopenhaver Doheny K, Alberto Travagli R. Stress adaptation upregulates oxytocin within hypothalamo-vagal neurocircuits. Neuroscience 2018; 390:198–205.
    1. Spear ET, Holt EA, Joyce EJ, et al. Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Neurogastroenterol Motil 2018; 30:e13349.
    1. Wunsch M, Jabari S, Voussen B, et al. The enteric nervous system is a potential autoimmune target in multiple sclerosis. Acta Neuropathol 2017; 134:281–295.
    1. Israelyan N, Margolis KG. Serotonin as a link between the gut-brain-microbiome axis in autism spectrum disorders. Pharmacol Res 2018; 132:1–6.
    1. McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics 2014; 133:872–883.
    1. Severance EG, Prandovszky E, Castiglione J, Yolken RH. Gastroenterology issues in schizophrenia: why the gut matters. Curr Psychiatry Rep 2015; 17:27.
    1. Pellegrini C, Colucci R, Antonioli L, et al. Intestinal dysfunction in Parkinson’s disease: lessons learned from translational studies and experimental models. Neurogastroenterol Motil 2016; 28:1781–1791.
    1. Travagli RA, Anselmi L. Vagal neurocircuitry and its influence on gastric motility. Nat Rev Gastroenterol Hepatol 2016; 13:389–401.
    1. Cersosimo MG, Benarroch EE. Neural control of the gastrointestinal tract: implications for Parkinson disease. Mov Disord 2008; 23: 1065–1075.
    1. Anselmi L, Toti L, Bove C, et al. A nigro-vagal pathway controls gastric motility and is affected in a rat model of Parkinsonism. Gastroenterology 2017; 153:1581–1593.This study describes a novel monosynaptic inputfromthe SNpc tothe dorsal vagal complex, which exerts a tonic modulatory role over gastric motility tone and is compromised in a rodent model of Parkisonism, providing further support to the hypothesis that idiopathic Parkinson’s disease may spread from the gastrointestinal tract in a retrograde manner.
    1. Braak H, Braak E. Pathoanatomy of Parkinson’s disease. J Neurol 2000; 247(Suppl 2):113–10.
    1. Braak H, Rub U, Gai WP, Del Tredici K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 2003; 110:517–536.
    1. Del Tredici K, Braak H. Review: sporadic Parkinson’s disease: development and distribution of α-synuclein pathology. Neuropathol Appl Neurobiol 2016; 42:33–50.

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