Central sensory-motor crosstalk in the neural gut-brain axis

  • Coltan G. Parker
    Affiliations
    Neuroscience Program, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana 61801, IL, USA
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  • Megan J. Dailey
    Affiliations
    Neuroscience Program, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana 61801, IL, USA

    Department of Food Sciences and Human Nutrition, University of Illinois at Urbana-Champaign, 905 South Goodwin Avenue, Urbana 61801, IL, USA
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  • Heidi Phillips
    Affiliations
    Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana 61802, IL, USA
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  • Elizabeth A. Davis
    Correspondence
    Corresponding author at: Department of Biological Sciences, University of Southern California, 3616 Trousdale Parkway, Los Angeles 90089, CA, USA.
    Affiliations
    Neuroscience Program, University of Illinois at Urbana-Champaign, 405 North Mathews Avenue, Urbana 61801, IL, USA
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Published:February 15, 2020DOI:https://doi.org/10.1016/j.autneu.2020.102656

      Highlights

      • Sensory and motor pathways of the gut-brain axis share common neurons in the brain.
      • These shared sensory-motor neurons exist in regions of the hind-, mid-, and forebrain.
      • Within nearly all regions assessed, ~50% of gut-brain neurons were sensory-motor neurons.
      • Central gut-brain neurons receiving sensory- or motor-only feedback were also observed.
      • These data provide an anatomical basis for sensory-motor feedback loops in the gut-brain axis.

      Abstract

      The neural gut-brain axis consists of viscerosensory and autonomic motor neurons innervating the gastrointestinal (GI) tract. Sensory neurons transmit nutrient-related and non-nutrient-related information to the brain, while motor neurons regulate GI motility and secretion. Previous research provides an incomplete picture of the brain nuclei that are directly connected with the neural gut-brain axis, and no studies have thoroughly assessed sensory-motor overlap in those nuclei. Our goal in this study was to comprehensively characterize the central sensory and motor circuitry associated with the neural gut-brain axis linked to a segment of the small intestine. We injected a retrograde (pseudorabies; PRV) and anterograde (herpes simplex virus 1; HSV) transsynaptic viral tracer into the duodenal wall of adult male rats. Immunohistochemical processing revealed single- and double-labeled cells that were quantified per nucleus. We found that across nearly all brain regions assessed, PRV + HSV immunoreactive neurons comprised the greatest percentage of labeled cells compared with single-labeled PRV or HSV neurons. These results indicate that even though sensory and motor information can be processed by separate neuronal populations, there is neuroanatomical evidence of direct sensory-motor feedback in the neural gut-brain axis throughout the entire caudal-rostral extent of the brain. This is the first study to exhaustively investigate the sensory-motor organization of the neural gut-brain axis, and is a step toward phenotyping the many central neuronal populations involved in GI control.

      Keywords

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      References

        • Benarroch E.E.
        Central autonomic control.
        in: Primer on the Autonomic Nervous System. Third edition. Elsevier, 2012: 9-12
        • Brittle E.E.
        • Reynolds A.E.
        • Enquist L.W.
        Two modes of pseudorabies virus neuroinvasion and lethality in mice.
        J. Virol. 2004; 78: 12951-12963
        • Brown T.A.
        • Washington M.C.
        • Metcalf S.A.
        • Sayegh A.I.
        The feeding responses evoked by cholecystokinin are mediated by vagus and splanchnic nerves.
        Peptides. 2011; 32: 1581-1586
        • Castle M.
        • Comoli E.
        • Loewy A.
        Autonomic brainstem nuclei are linked to the hippocampus.
        Neuroscience. 2005; 134: 657-669
        • Catani M.
        A little man of some importance.
        Brain. 2017; 140: 3055-3061
        • Davis E.A.
        • Washington M.C.
        • Yaniz E.R.
        • Phillips H.
        • Sayegh A.I.
        • Dailey M.J.
        Long-term effect of parasympathetic or sympathetic denervation on intestinal epithelial cell proliferation and apoptosis.
        Exp. Biol. Med. (Maywood). 2017; 242: 1499-1507
        • Ferguson A.V.
        • Latchford K.J.
        • Samson W.K.
        The paraventricular nucleus of the hypothalamus–a potential target for integrative treatment of autonomic dysfunction.
        Expert Opin. Ther. Targets. 2008; 12: 717-727
        • Hunt J.V.
        • Washington M.C.
        • Sayegh A.I.
        Exenatide and feeding: possible peripheral neuronal pathways.
        Peptides. 2012; 33: 285-290
        • Jansen A.S.
        • Nguyen X.V.
        • Karpitskiy V.
        • Mettenleiter T.C.
        • Loewy A.D.
        Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response.
        Science (New York, N.Y.). 1995; 270: 644-646
        • Jones E.G.
        • Peters A.
        Sensory-Motor Areas and Aspects of Cortical Connectivity: Volume 5: Sensory-Motor Areas and Aspects of Cortical Connectivity.
        Springer Science & Business Media, 2012
        • Kalia M.
        • Sullivan J.M.
        Brainstem projections of sensory and motor components of the vagus nerve in the rat.
        J. Comp. Neurol. 1982; 211: 248-265
        • Kim J.-S.
        • Enquist L.W.
        • Card J.P.
        Circuit-specific coinfection of neurons in the rat central nervous system with two pseudorabies virus recombinants.
        J. Virol. 1999; 73: 9521-9531
        • Kobiler O.
        • Lipman Y.
        • Therkelsen K.
        • Daubechies I.
        • Enquist L.W.
        Herpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes.
        Nat. Commun. 2010; 1: 146
        • Kramer T.
        • Enquist L.W.
        Directional spread of alphaherpesviruses in the nervous system.
        Viruses. 2013; 5: 678-707
        • Loewy A.D.
        • Spyer K.M.
        Central Regulation of Autonomic Functions.
        Oxford University Press, 1990
        • Magalha B.
        • Saraiva P.
        Sensory and motor representation in the cerebral cortex of the marsupial Didelphis azarae azarae.
        Brain Res. 1971; 34: 291-299
        • Nunn N.
        • Womack M.
        • Dart C.
        • Barrett-Jolley R.
        Function and pharmacology of spinally-projecting sympathetic pre-autonomic neurones in the paraventricular nucleus of the hypothalamus.
        Curr. Neuropharmacol. 2011; 9: 262-277
        • O’Hare J.D.
        • Zsombok A.
        CNS control of metabolism: brain-liver connections: role of the preautonomic PVN neurons.
        Am. J. Physiol. Endocrinol. Metab. 2016; 310: E183
        • Paxinos G.
        • Watson C.
        The Rat Brain in Stereotaxic Coordinates.
        7th Edition ed. Academic Press, 2014
        • Pickard G.E.
        • Smeraski C.A.
        • Tomlinson C.C.
        • Banfield B.W.
        • Kaufman J.
        • Wilcox C.L.
        • Enquist L.W.
        • Sollars P.J.
        Intravitreal injection of the attenuated pseudorabies virus PRV Bartha results in infection of the hamster suprachiasmatic nucleus only by retrograde transsynaptic transport via autonomic circuits.
        J. Neurosci. 2002; 22: 2701-2710
        • Rinaman L.
        • Schwartz G.
        Anterograde transneuronal viral tracing of central viscerosensory pathways in rats.
        J. Neurosci. 2004; 24: 2782-2786
        • Ryu V.
        • Bartness T.J.
        Short and long sympathetic-sensory feedback loops in white fat.
        Am. J. Phys. Regul. Integr. Comp. Phys. 2014; 306: R886-R900
        • Ryu V.
        • Garretson J.T.
        • Liu Y.
        • Vaughan C.H.
        • Bartness T.J.
        Brown adipose tissue has sympathetic-sensory feedback circuits.
        J. Neurosci. 2015; 35: 2181-2190
        • Song C.K.
        • Enquist L.W.
        • Bartness T.J.
        New developments in tracing neural circuits with herpesviruses.
        Virus Res. 2005; 111: 235-249
        • Song C.K.
        • Vaughan C.H.
        • Keen-Rhinehart E.
        • Harris R.B.
        • Richard D.
        • Bartness T.J.
        Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence.
        Am. J. Phys. Regul. Integr. Comp. Phys. 2008; 295: R417-R428
        • Spencer N.J.
        • Kyloh M.
        • Duffield M.
        Identification of different types of spinal afferent nerve endings that encode noxious and innocuous stimuli in the large intestine using a novel anterograde tracing technique.
        PLoS One. 2014; 9e112466
        • Spencer N.J.
        • Zagorodnyuk V.P.
        • Brookes S.J.
        • Hibberd T.
        Spinal afferent nerve endings in visceral organs: recent advances.
        Am. J. Physiol. Gastrointest. Liver Physiol. 2017; 311: G1056-G1063
        • Suarez A.N.
        • Hsu T.M.
        • Liu C.M.
        • Noble E.E.
        • Cortella A.M.
        • Nakamoto E.M.
        • Hahn J.D.
        • de Lartigue G.
        • Kanoski S.E.
        Gut vagal sensory signaling regulates hippocampus function through multi-order pathways.
        Nat. Commun. 2018; 9: 2181
        • Sullivan C.N.
        • Raboin S.J.
        • Gulley S.
        • Sinzobahamvya N.T.
        • Green G.M.
        • Reeve Jr., J.R.
        • Sayegh A.I.
        Endogenous cholecystokinin reduces food intake and increases Fos-like immunoreactivity in the dorsal vagal complex but not in the myenteric plexus by CCK1 receptor in the adult rat.
        Am. J. Physiol. Regul. Integr. Comp. Physiol. 2007; 292: R1071-R1080
        • Taylor M.P.
        • Kobiler O.
        • Enquist L.W.
        Alphaherpesvirus axon-to-cell spread involves limited virion transmission.
        Proc. Natl. Acad. Sci. 2012; 109: 17046-17051
        • Wojaczynski G.J.
        • Engel E.A.
        • Steren K.E.
        • Enquist L.W.
        • Card P.J.
        The neuroinvasive profiles of H129 (herpes simplex virus type 1) recombinants with putative anterograde-only transneuronal spread properties.
        Brain Struct. Funct. 2015; 220: 1395-1420
        • Yox D.P.
        • Stokesberry H.
        • Ritter R.C.
        Vagotomy attenuates suppression of sham feeding induced by intestinal nutrients.
        Am. J. Phys. 1991; 260: R503-R508