Colonic dilation and altered ex vivo gastrointestinal motility in the neuroligin-3 knockout mouse

Gastrointestinal (GI) dysfunction is commonly reported by people diagnosed with autism spectrum disorder (ASD; autism) but the cause is unknown. Mutations in genes encoding synaptic proteins including Neuroligin-3 are associated with autism. Mice lacking Neuroligin-3 (Nlgn3 -/- ) have altered brain function, but whether the enteric nervous system (ENS) is altered remains unknown. We assessed for changes in GI structure and function in Nlgn3 -/- mice. We found no significant morphological differences in villus height or crypt depth in the jejunum or colon between wildtype (WT) and Nlgn3 -/- mice. To determine whether deletion of Nlgn3 affects enteric neurons, we stained for neural markers in the myenteric plexus. Nlgn3 -/- mice had similar numbers of neurons expressing the pan-neuronal marker Hu in the jejunum, proximal mid, and distal colon regions. We also found no differences in the number of neuronal nitric oxide synthase (nNOS+) or calretinin (CalR+) motor neurons and interneurons between WT and Nlgn3 -/- mice. We used ex vivo video imaging analysis to assess colonic motility under baseline conditions and observed faster colonic migrating motor complexes (CMMCs) and an increased colonic diameter in Nlgn3 -/- mice, although CMMC frequency was unchanged. At baseline, CMMCs were faster in Nlgn3 -/- mice compared to WT. Although the numbers of neuronal subsets are conserved in Nlgn3 -/- mice, these findings suggest that Neuroligin-3 modulates inhibitory neural pathways in the ENS and may contribute to mechanisms underlying GI disorders in autism. Autism Res 2019. © 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. Lay Summary: People with autism commonly experience gut problems. Many gene mutations associated with autism affect neuronal activity. We studied mice in w