Evidence map›Paper›PMID 37772988›Full record

ArticleThe Journal of physiology2023

The substantia nigra modulates proximal colon tone and motility in a vagally-dependent manner in the rat.

Tiaosi Xing, Giorgia Nanni, Cameron R Burkholder, Kirsteen N Browning, R Alberto Travagli

Open access · hybridAbstract read
In one paragraph

Article in The Journal of physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
  3. Gastrointestinal dysmotility in rodent models of Parkinson's disease.American journal of physiology. Gastrointestinal and liver physiology · 2024
    Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Tiaosi XingDepartment of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA.
Giorgia NanniDepartment of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA.
Cameron R BurkholderDepartment of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA.ORCID 0000-0002-5062-3703
Kirsteen N BrowningDepartment of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA.
R Alberto TravagliNeurobiology Research, Newport, NC, USA.ORCID 0000-0002-4901-1558
Penn State Milton S. Hershey Medical Center · USInstitute of Neurobiology · BG

Funding

BRAINSTEM CIRCUITS CONTROLLING GASTROINTESTINAL FUNCTIONR01DK055530 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BROWNING, KIRSTEEN NAIRN · 1998 to 2020
$4.6M
Gut-brain axis in Parkinson's diseaseR01DK124098 · NIDDK · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI BROWNING, KIRSTEEN NAIRN, SUBRAMANIAN, THYAGARAJAN · 2020 to 2025
$2.6M
NIDDK NIH HHS R01 DK055530NIDDK NIH HHS R01 DK124098
6 · The paper itself

Abstract

A monosynaptic pathway connects the substantia nigra pars compacta (SNpc) to neurons of the dorsal motor nucleus of the vagus (DMV). This monosynaptic pathway modulates the vagal control of gastric motility. It is not known, however, whether this nigro-vagal pathway also modulates the tone and motility of the proximal colon. In rats, microinjection of retrograde tracers in the proximal colon and of anterograde tracers in SNpc showed that bilaterally labelled colonic-projecting neurons in the DMV received inputs from SNpc neurons. Microinjections of the ionotropic glutamate receptor agonist, NMDA, in the SNpc increased proximal colonic motility and tone, as measured via a strain gauge aligned with the colonic circular smooth muscle; the motility increase was inhibited by acute subdiaphragmatic vagotomy. Upon transfection of SNpc with pAAV-hSyn-hM3D(Gq)-mCherry, chemogenetic activation of nigro-vagal nerve terminals by brainstem application of clozapine-N-oxide increased the firing rate of DMV neurons and proximal colon motility; both responses were abolished by brainstem pretreatment with the dopaminergic D1-like antagonist SCH23390. Chemogenetic inhibition of nigro-vagal nerve terminals following SNpc transfection with pAAV-hSyn-hM4D(Gi)-mCherry decreased the firing rate of DMV neurons and inhibited proximal colon motility. These data suggest that a nigro-vagal pathway modulates activity of the proximal colon motility tonically via a discrete dopaminergic synapse in a manner dependent on vagal efferent nerve activity. Impairment of this nigro-vagal pathway may contribute to the severely reduced colonic transit and prominent constipation observed in both patients and animal models of parkinsonism. KEY POINTS: Substantia nigra pars compacta (SNpc) neurons are connected to the dorsal motor nucleus of the vagus (DMV) neurons via a presumed direct pathway. Brainstem neurons in the lateral DMV innervate the proximal colon. Colonic-projecting DMV neurons receive inputs from neurons of the SNpc. The nigro-vagal pathway modulates tone and motility of the proximal colon via D1-like receptors in the DMV. The present study provides the mechanistic basis for explaining how SNpc alterations may lead to a high rate of constipation in patients with Parkinson's Disease.

Indexed as

StomachSubstantia NigraAnimalsColonConstipationGastrointestinal MotilityHumansRatsRats, Sprague-DawleyVagus Nervebrain stemdorsal motor nucleus of the vagusproximal colon motilitysubstantia nigra pars compacta

Identifiers

PMID37772988
PMCPMC10873099
OpenAlexW4387157536

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.