Refining Enteric Neural Circuitry by Quantitative Morphology and Function in Mice

RNA-Seq, electrophysiology and optogenetics in mouse models are used to assess function, identify disease related genes and model enteric neural circuits. Lacking a comprehensive quantitative description of the murine colonic enteric nervous system (ENS) makes it difficult to most effectively use mouse data to better understand ENS function or for development of therapeutic approaches for human motility disorders. Our goal was to provide a quantitative description of mouse colon to establish the extent to which mouse colon architecture, connectivity and function is a useful surrogate for human and other mammalian ENS. Using GCaMP imaging coupled with pharmacology and quantitative confocal and 3D image reconstruction, we present quantitative and functional data demonstrating that regional structural changes and variable distribution of neurons define neural circuit dynamics and functional connectivity responsible for colonic motor patterns and regional functional differences. Our results advance utility of multispecies and gut region-specific data.