{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:49Z","timestamp":1787028529351,"version":"build-2736575974"},"reference-count":74,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["FT160100126"],"award-info":[{"award-number":["FT160100126"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["GNT1158952"],"award-info":[{"award-number":["GNT1158952"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["FT160100126"],"award-info":[{"award-number":["FT160100126"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1158952"],"award-info":[{"award-number":["GNT1158952"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Individuals with autism often experience gastrointestinal issues but the cause is unknown. Many gene mutations that modify neuronal synapse function are associated with autism and therefore may impact the enteric nervous system that regulates gastrointestinal function. A missense mutation in the Nlgn3 gene encoding the cell adhesion protein Neuroligin-3 was identified in two brothers with autism who both experienced severe gastrointestinal dysfunction. Mice expressing this mutation (Nlgn3R451C mice) are a well-studied preclinical model of autism and show autism-relevant characteristics, including impaired social interaction and communication, as well as repetitive behaviour. We previously showed colonic dysmotility in response to GABAergic inhibition and increased myenteric neuronal numbers in the small intestine in Nlgn3R451C mice bred on a mixed genetic background. Here, we show that gut dysfunction is a persistent phenotype of the Nlgn3 R451C mutation in mice backcrossed onto a C57BL\/6 background. We report that Nlgn3R451C mice show a 30.9% faster gastrointestinal transit (p = 0.0004) in vivo and have 6% longer small intestines (p = 0.04) compared to wild-types due to a reduction in smooth muscle tone. In Nlgn3R451C mice, we observed a decrease in resting jejunal diameter (proximal jejunum: 10.6% decrease, p = 0.02; mid: 9.8%, p = 0.04; distal: 11.5%, p = 0.009) and neurally regulated dysmotility as well as shorter durations of contractile complexes (mid: 25.6% reduction in duration, p = 0.009; distal: 30.5%, p = 0.004) in the ileum. In Nlgn3R451C mouse colons, short contractions were inhibited to a greater extent (57.2% by the GABAA antagonist, gabazine, compared to 40.6% in wild-type mice (p = 0.007). The inhibition of nitric oxide synthesis decreased the frequency of contractile complexes in the jejunum (WT p = 0.0006, Nlgn3R451C\u00a0p = 0.002), but not the ileum, in both wild-type and Nlgn3R451C mice. These findings demonstrate that changes in enteric nervous system function contribute to gastrointestinal dysmotility in mice expressing the autism-associated R451C missense mutation in the Neuroligin-3 protein.<\/jats:p>","DOI":"10.3390\/ijms25020832","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T07:50:48Z","timestamp":1704873048000},"page":"832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Faster Gastrointestinal Transit, Reduced Small Intestinal Smooth Muscle Tone and Dysmotility in the Nlgn3R451C Mouse Model of Autism"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8569-2912","authenticated-orcid":false,"given":"Suzanne","family":"Hosie","sequence":"first","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7884-5324","authenticated-orcid":false,"given":"Tanya","family":"Abo-Shaban","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mou","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri K.","family":"Balasuriya","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"},{"name":"Graduate School of Medicine, Kobe University, Kobe 657-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitra","family":"Mohsenipour","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed U.","family":"Alamoudi","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"},{"name":"Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon T.","family":"Filippone","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne, VIC 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle T.","family":"Belz","sequence":"additional","affiliation":[{"name":"Frazer Institute, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1664-6060","authenticated-orcid":false,"given":"Ashley E.","family":"Franks","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Life Sciences, La Trobe University, Melbourne, VIC 3083, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-7717","authenticated-orcid":false,"given":"Joel C.","family":"Bornstein","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2597-6929","authenticated-orcid":false,"given":"Kulmira","family":"Nurgali","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne, VIC 3021, Australia"},{"name":"Department of Medicine Western Health, University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Regenerative Medicine and Stem Cells Program, Australian Institute for Musculoskeletal Science (AIMSS), Melbourne, VIC 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-7198","authenticated-orcid":false,"given":"Elisa L.","family":"Hill-Yardin","sequence":"additional","affiliation":[{"name":"School of Health and Biomedical Sciences, STEM College, RMIT University, Melbourne, VIC 3083, Australia"},{"name":"Department of Anatomy and Physiology, University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cpr.2009.01.003","article-title":"Anxiety in children and adolescents with autism spectrum disorders","volume":"29","author":"White","year":"2009","journal-title":"Clin. Psychol. Review."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.2147\/NDT.S84585","article-title":"Aggression in autism spectrum disorder: Presentation and treatment options","volume":"2016","author":"Fitzpatrick","year":"2016","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1542\/peds.2013-3995","article-title":"Gastrointestinal symptoms in autism spectrum disorder: A meta-analysis","volume":"133","author":"McElhanon","year":"2014","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s10803-018-3767-7","article-title":"Development of a brief parent-report screen for common gastrointestinal disorders in autism spectrum disorder","volume":"49","author":"Margolis","year":"2019","journal-title":"J. Autism Dev. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1542\/peds.2009-1878C","article-title":"Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: A consensus report","volume":"125 (Supp. 1)","author":"Buie","year":"2010","journal-title":"Pediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S160","DOI":"10.1542\/peds.2012-0900N","article-title":"Gastrointestinal conditions in children with autism spectrum disorder: Developing a research agenda","volume":"130 (Supp. 2)","author":"Coury","year":"2012","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kohane, I.S., McMurry, A., Weber, G., MacFadden, D., Rappaport, L., Kunkel, L., Bickel, J., Wattanasin, N., Spence, S., and Murphy, S. (2012). The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033224"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1097\/MPG.0b013e3181dcc4a5","article-title":"Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives","volume":"51","author":"Familiari","year":"2010","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.biopsych.2020.09.025","article-title":"Plasma and fecal metabolite profiles in autism spectrum disorder","volume":"89","author":"Needham","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.cell.2019.05.004","article-title":"Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice","volume":"177","author":"Sharon","year":"2019","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10158","DOI":"10.1038\/s41598-022-14077-1","article-title":"SFARI genes and where to find them; modelling Autism Spectrum Disorder specific gene expression dysregulation with RNA-seq data","volume":"12","author":"Arpi","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13764","DOI":"10.1073\/pnas.1111093108","article-title":"Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function","volume":"108","author":"Etherton","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/s41593-019-0445-9","article-title":"Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice","volume":"22","author":"Guo","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fncel.2018.00234","article-title":"Altered Amygdala Excitation and CB1 Receptor Modulation of Aggressive Behavior in the Neuroligin-3(R451C) Mouse Model of Autism","volume":"12","author":"Hosie","year":"2018","journal-title":"Front. Cell Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nature09965","article-title":"Shank3 mutant mice display autistic-like behaviours and striatal dysfunction","volume":"472","author":"Feliciano","year":"2011","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.cell.2014.04.045","article-title":"Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors","volume":"158","author":"Rothwell","year":"2014","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nature11015","article-title":"Autistic-like behaviours and hyperactivity in mice lacking ProSAP1\/Shank2","volume":"486","author":"Schmeisser","year":"2012","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.1146221","article-title":"A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice","volume":"318","author":"Tabuchi","year":"2007","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"699315","DOI":"10.3389\/fncel.2021.699315","article-title":"A temporal activity of CA1 neurons underlying short-term memory for social recognition altered in PTEN mouse models of autism spectrum disorder","volume":"15","author":"Chai","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.neuron.2013.02.036","article-title":"Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling","volume":"78","author":"Malenka","year":"2013","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.neubiorev.2019.04.012","article-title":"Behavioral neuroscience of autism","volume":"110","author":"Takumi","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14681","DOI":"10.1523\/JNEUROSCI.1666-15.2015","article-title":"Selective dysregulation of hippocampal inhibition in the mouse lacking autism candidate gene CNTNAP2","volume":"35","author":"Jurgensen","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"470","DOI":"10.3389\/fncel.2018.00470","article-title":"Synaptopathology involved in autism spectrum disorder","volume":"12","author":"Guang","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/aur.2127","article-title":"Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3","volume":"12","author":"Hosie","year":"2019","journal-title":"Autism Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"James, D.M., Davidson, E.A., Yanes, J., Moshiree, B., and Dallman, J.E. (2021). The Gut-Brain-Microbiome Axis and Its Link to Autism: Emerging Insights and the Potential of Zebrafish Models. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.662916"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.bbi.2020.05.072","article-title":"Autism-associated synaptic mutations impact the gut-brain axis in mice","volume":"88","author":"Lee","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12687","DOI":"10.1038\/s41598-023-39555-y","article-title":"Impaired cecal motility and secretion alongside expansion of gut-associated lymphoid tissue in the Nlgn3(R451C) mouse model of autism","volume":"13","author":"Lee","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sauer, A.K., Bockmann, J., Steinestel, K., Boeckers, T.M., and Grabrucker, A.M. (2019). Altered Intestinal Morphology and Microbiota Composition in the Autism Spectrum Disorders Associated SHANK3 Mouse Model. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092134"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fncel.2020.00085","article-title":"Altered Caecal Neuroimmune Interactions in the Neuroligin-3(R451C) Mouse Model of Autism","volume":"14","author":"Sharna","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbi.2013.12.005","article-title":"Altered gut microbiota and activity in a murine model of autism spectrum disorders","volume":"37","author":"Wopereis","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1172\/JCI84877","article-title":"Serotonin transporter variant drives preventable gastrointestinal abnormalities in development and function","volume":"126","author":"Margolis","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.neuron.2018.11.018","article-title":"Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder","volume":"101","author":"Sgritta","year":"2019","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.cell.2014.06.017","article-title":"Disruptive CHD8 mutations define a subtype of autism early in development","volume":"158","author":"Bernier","year":"2014","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1126\/science.1224159","article-title":"Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism","volume":"338","author":"Baudouin","year":"2012","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1111\/j.1460-9568.2007.05842.x","article-title":"Neuroligin-3 is a neuronal adhesion protein at GABAergic and glutamatergic synapses","volume":"26","author":"Budreck","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8589","DOI":"10.1074\/jbc.AC120.012571","article-title":"Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus","volume":"295","author":"Uchigashima","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Herath, M., Cho, E., Marklund, U., Franks, A.E., Bornstein, J.C., and Hill-Yardin, E.L. (2023). Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal-Glial Synapses and Reduced Expression in Nlgn3(R451C) Mice. Biomolecules, 13.","DOI":"10.1101\/2022.05.02.490237"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/glia.1050","article-title":"Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia","volume":"34","author":"Gilbert","year":"2001","journal-title":"Glia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng1136","article-title":"Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism","volume":"34","author":"Jamain","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"22365","DOI":"10.1074\/jbc.M410723200","article-title":"Dissection of synapse induction by neuroligins: Effect of a neuroligin mutation associated with autism","volume":"280","author":"Chubykin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4889","DOI":"10.1523\/JNEUROSCI.0468-04.2004","article-title":"The Arg451Cys-neuroligin-3 mutation associated with autism reveals a defect in protein processing","volume":"24","author":"Comoletti","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13229-015-0055-7","article-title":"A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice","volume":"6","author":"Burrows","year":"2015","journal-title":"Mol. Autism"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/aur.22","article-title":"Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice","volume":"1","author":"Chadman","year":"2008","journal-title":"Autism Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Herath, M., Bornstein, J.C., Hill-Yardin, E.L., and Franks, A.E. (2022). The autism-associated Neuroligin-3 R451C mutation alters mucus density and the spatial distribution of bacteria in the mouse gastrointestinal tract. bioRxiv, bioRxiv:06.27.497808.","DOI":"10.1101\/2022.06.27.497808"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"102854","DOI":"10.1016\/j.autneu.2021.102854","article-title":"The role of enteric inhibitory neurons in intestinal motility","volume":"235","author":"Costa","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/j.1469-7793.1999.0575t.x","article-title":"Quantitative analysis of peristalsis in the guinea-pig small intestine using spatio-temporal maps","volume":"517 (Pt. 2)","author":"Hennig","year":"1999","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1113\/jphysiol.2008.160416","article-title":"Strain-specific genetics, anatomy and function of enteric neural serotonergic pathways in inbred mice","volume":"587","author":"Neal","year":"2009","journal-title":"J. Physiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"G624","DOI":"10.1152\/ajpgi.00354.2001","article-title":"Somatostatin sst(2) receptors inhibit peristalsis in the rat and mouse jejunum","volume":"282","author":"Abdu","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"G99","DOI":"10.1152\/ajpgi.00185.2019","article-title":"Neural motor complexes propagate continuously along the full length of mouse small intestine and colon","volume":"318","author":"Costa","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"G1043","DOI":"10.1152\/ajpgi.00205.2005","article-title":"Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine","volume":"289","author":"Seerden","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"647555","DOI":"10.3389\/fnins.2021.647555","article-title":"Nitric Oxide Regulates Estrus Cycle Dependent Colonic Motility in Mice","volume":"15","author":"Balasuriya","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/aur.2109","article-title":"Colonic dilation and altered ex vivo gastrointestinal motility in the Neuroligin-3 knockout mouse","volume":"13","author":"Leembruggen","year":"2020","journal-title":"Autism Res."},{"key":"ref_53","first-page":"53828","article-title":"Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice","volume":"108","author":"Swaminathan","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Abo-Shaban, T., Lee, C.Y.Q., Hosie, S., Balasuriya, G.K., Mohsenipour, M., Johnston, L.A., and Hill-Yardin, E.L. (2023). GutMap: A New Interface for Analysing Regional Motility Patterns in ex vivo Mouse Gastrointestinal Preparations. Bio Protoc., 13.","DOI":"10.21769\/BioProtoc.4831"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10361","DOI":"10.1523\/JNEUROSCI.0441-14.2014","article-title":"Molecular and functional diversity of GABA-A receptors in the enteric nervous system of the mouse colon","volume":"34","author":"Seifi","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3389\/fphys.2018.00097","article-title":"Neurally Released GABA Acts via GABA(C) Receptors to Modulate Ca(2+) Transients Evoked by Trains of Synaptic Inputs, but Not Responses Evoked by Single Stimuli, in Myenteric Neurons of Mouse Ileum","volume":"9","author":"Koussoulas","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s004410050565","article-title":"Chemical coding of neurons in the myenteric plexus and external muscle of the small and large intestine of the mouse","volume":"284","author":"Sang","year":"1996","journal-title":"Cell Tissue Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S151","DOI":"10.1007\/s10995-012-1004-0","article-title":"Parent-reported prevalence of autism spectrum disorders in US-born children: An assessment of changes within birth cohorts from the 2003 to the 2007 National Survey of Children\u2019s Health","volume":"16","author":"Schieve","year":"2012","journal-title":"Matern. Child Health J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1111\/nmo.12890","article-title":"Gastrointestinal dysfunction and enteric neurotoxicity following treatment with anticancer chemotherapeutic agent 5-fluorouracil","volume":"28","author":"McQuade","year":"2016","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/bph.14114","article-title":"Oxaliplatin-induced enteric neuronal loss and intestinal dysfunction is prevented by co-treatment with BGP-15","volume":"175","author":"McQuade","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3389\/fphys.2017.00391","article-title":"Irinotecan-Induced Gastrointestinal Dysfunction Is Associated with Enteric Neuropathy, but Increased Numbers of Cholinergic Myenteric Neurons","volume":"8","author":"McQuade","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"G85","DOI":"10.1152\/ajpgi.00210.2016","article-title":"Alterations of colonic function in the Winnie mouse model of spontaneous chronic colitis","volume":"312","author":"Robinson","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1093\/ibd\/izaa161","article-title":"Inhibition of APE1\/Ref-1 Redox Signaling Alleviates Intestinal Dysfunction and Damage to Myenteric Neurons in a Mouse Model of Spontaneous Chronic Colitis","volume":"27","author":"Sahakian","year":"2021","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.nbd.2014.12.014","article-title":"Early inflammatory damage to intestinal neurons occurs via inducible nitric oxide synthase","volume":"75","author":"Venkataramana","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1038\/ncomms4326","article-title":"The origin of segmentation motor activity in the intestine","volume":"5","author":"Huizinga","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41575-020-0271-2","article-title":"Enteric nervous system: Sensory transduction, neural circuits and gastrointestinal motility","volume":"17","author":"Spencer","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0092-8674(00)81053-3","article-title":"Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains","volume":"84","author":"Brenman","year":"1996","journal-title":"Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.pnpbp.2017.11.016","article-title":"PSD95: A synaptic protein implicated in schizophrenia or autism?","volume":"82","author":"Coley","year":"2018","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1126\/science.277.5331.1511","article-title":"Binding of neuroligins to PSD-95","volume":"277","author":"Irie","year":"1997","journal-title":"Science"},{"key":"ref_70","first-page":"7","article-title":"An experimental method to identify neurogenic and myogenic active mechanical states of intestinal motility","volume":"11","author":"Costa","year":"2013","journal-title":"Front. Syst. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s11894-013-0363-z","article-title":"Interstitial cells of Cajal: Update on basic and clinical science","volume":"16","author":"Huizinga","year":"2014","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1152\/ajpgi.90380.2008","article-title":"Gut peristalsis is governed by a multitude of cooperating mechanisms","volume":"296","author":"Huizinga","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev.physiol.68.040504.094718","article-title":"Interstitial cells of Cajal as pacemakers in the gastrointestinal tract","volume":"68","author":"Sanders","year":"2006","journal-title":"Annu. Rev. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"133","DOI":"10.5056\/jnm19029","article-title":"Spatiotemporal Mapping Reveals Regional Gastrointestinal Dysfunction in mdx Dystrophic Mice Ameliorated by Oral L-arginine Supplementation","volume":"26","author":"Swiderski","year":"2020","journal-title":"J. Neurogastroenterol. Motil."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/832\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:43:16Z","timestamp":1760103796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,9]]},"references-count":74,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25020832"],"URL":"https:\/\/doi.org\/10.3390\/ijms25020832","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,9]]}}}