Strain‐specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice

Neal, Kathleen Bronwyn; Parry, Laura J.; Bornstein, Joel C.

doi:10.1113/jphysiol.2008.160416

Cited by 113 publications

(110 citation statements)

References 73 publications

(108 reference statements)

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“…Because serotonin (5-HT) acts on the ENS to modulate gastrointestinal function in mice 6 we analyzed motility patterns in response to the 5-HT 3/4 receptor antagonist tropisetron in colonic preparations from WT and NL3 R451C mice.…”

Section: Representative Resultsmentioning

confidence: 99%

“…This technique has been used to identify strain differences in small intestinal function; differential sensitivity to 5-HT 3 and 5-HT 4 antagonists were observed in the jejunum of Balb/c and C57/Bl6 mice due to the polymorphic nature of the tph2 gene expressed in the two strains 6 . The effect of 5-HT inhibition on motility remains controversial, as conflicting data has been reported on the importance of endogenous 5-HT on colonic peristalsis and CMMCs 14,15 .…”

Section: Introductionmentioning

confidence: 99%

“…Colonic migrating motor complexes (CMMCs) are spontaneous, neurogenic events that are the predominant motor pattern observed in isolated mouse colon in the absence of fecal pellets [4][5][6][7][8][9] . CMMCs are defined as rhythmic contractions that propagate along a horizontal distance that is at least half the total length of the colon (i.e., from the cecum to the rectum) 10 .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, this method is suitable for analyzing small intestinal segmentation during the fed state 6,23 . The ex vivo nature of this method enables the role of the enteric nervous system to be assessed in the absence of central nervous system inputs and is therefore an ideal way to investigate gastrointestinal motility in a variety of models, including genetic models of disease (see Figure 2) 6,34 . This method can also be used to compare physiological data to computer simulations of motor activity 23,33,35 .…”

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Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

Swaminathan

Hill‐Yardin

Ellis

et al. 2016

JoVE

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The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central nervous system. Changes in ENS function are a major cause of GI symptoms and disease and may contribute to GI symptoms reported in neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure to analyze the enteric neural regulation of CMMCs in ex vivo preparations of mouse colon is described. The colon is dissected from the animal and flushed to remove fecal content prior to being cannulated in an organ bath. Data is acquired via a video camera positioned above the organ bath and converted to high-resolution spatiotemporal maps via an inhouse software package. Using this technique, baseline contractile patterns and pharmacological effects on ENS function in colon segments can be compared over 3-4 hr. In addition, propagation length and speed of CMMCs can be recorded as well as changes in gut diameter and contraction frequency. This technique is useful for characterizing gastrointestinal motility patterns in transgenic mouse models (and in other species including rat and guinea pig). In this way, pharmacologically induced changes in CMMCs are recorded in wild type mice and in the Neuroligin-3 R451C mouse model of autism. Furthermore, this technique can be applied to other regions of the GI tract including the duodenum, jejunum and ileum and at different developmental ages in mice. Video LinkThe video component of this article can be found at

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Section: Representative Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

Swaminathan

Hill‐Yardin

Ellis

et al. 2016

JoVE

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“…Источниками серотонина в кишечнике служат как энтерохромафин-ные клетки, так и и нейроны энтеральной нервной системы, что убедительно пока-зано рядом авторов [1,2,3]. В клиниче-ской практике серотонин и его агонисты в последнее время находят широкое приме-нение [4,5], что повышает актуальность проведенного нами исследования.…”

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Serotoninergic structures strengthens vagal responses of the duodenum

Sveshnikov¹,

Сергеевич²,

Smirnov³

et al. 2011

I.P. Pavlov Russian Medical Biological Herald

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Gastrointestinal dysfunction in patients and mice expressing the autism‐associated R451C mutation in neuroligin‐3

et al. 2019

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Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin‐3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin‐3 R451C missense mutation (NL3 R451C ). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3 R451C compared to wild‐type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABA A receptor modulation in NL3 R451C mice, a well‐established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3 R451C mice. Although we observed altered sensitivity to GABA A receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA‐immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3 R451C mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3 R451C mice as a useful preclinical model of GI dysfunction in autism. Autism Res 2019, 12: 1043–1056 . © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary People with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism‐associated R451C mutation encoding the neuroligin‐3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin‐3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication.

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Strain‐specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice

Cited by 113 publications

References 73 publications

Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

Serotoninergic structures strengthens vagal responses of the duodenum

Gastrointestinal dysfunction in patients and mice expressing the autism‐associated R451C mutation in neuroligin‐3

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