224 a Nigro-Vagal Pathway Controls Colonic Motility and May Be Impaired in a Model of Environmental Parkinson's Disease.

Nanni, Giorgia; Travagli, R. Alberto

doi:10.1016/s0016-5085(20)30785-x

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“…Preliminary accounts of the present work have been presented at the 2020 Digestive Disease Week (Nanni & Travagli, 2020).…”

Section: Introductionmentioning

confidence: 99%

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

Xing,

Nanni,

Burkholder

et al. 2023

The Journal of Physiology

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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. imageKey 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.

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“…Preliminary accounts of the present work have been presented at the 2020 Digestive Disease Week (Nanni & Travagli, 2020).…”

Section: Introductionmentioning

confidence: 99%

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

Xing,

Nanni,

Burkholder

et al. 2023

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

224 a Nigro-Vagal Pathway Controls Colonic Motility and May Be Impaired in a Model of Environmental Parkinson's Disease.

Cited by 1 publication

References 0 publications

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

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

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