All Publications

  • Regional cytoarchitecture of the adult and developing mouse enteric nervous system. Current biology : CB Hamnett, R., Dershowitz, L. B., Sampathkumar, V., Wang, Z., Gomez-Frittelli, J., De Andrade, V., Kasthuri, N., Druckmann, S., Kaltschmidt, J. A. 2022


    The organization and cellular composition of tissues are key determinants of their biological function. In the mammalian gastrointestinal (GI) tract, the enteric nervous system (ENS) intercalates between muscular and epithelial layers of the gut wall and can control GI function independent of central nervous system (CNS) input.1 As in the CNS, distinct regions of the GI tract are highly specialized and support diverse functions, yet the regional and spatial organization of the ENS remains poorly characterized.2 Cellular arrangements,3,4 circuit connectivity patterns,5,6 and diverse cell types7-9 are known to underpin ENS functional complexity and GI function, but enteric neurons are most typically described only as a uniform meshwork of interconnected ganglia. Here, we present a bird's eye view of the mouse ENS, describing its previously underappreciated cytoarchitecture and regional variation. We visually and computationally demonstrate that enteric neurons are organized in circumferential neuronal stripes. This organization emerges gradually during the perinatal period, with neuronal stripe formation in the small intestine (SI) preceding that in the colon. The width of neuronal stripes varies throughout the length of the GI tract, and distinct neuronal subtypes differentially populate specific regions of the GI tract, with stark contrasts between SI and colon as well as within subregions of each. This characterization provides a blueprint for future understanding of region-specific GI function and identifying ENS structural correlates of diverse GI disorders.

    View details for DOI 10.1016/j.cub.2022.08.030

    View details for PubMedID 36070775

  • COUNTEN, an AI-Driven Tool for Rapid and Objective Structural Analyses of the Enteric Nervous System. eNeuro Kobayashi, Y., Bukowski, A., Das, S., Espenel, C., Gomez-Fritteli, J., Wagle, N., Bakshi, S., Saha, M., Kaltschmidt, J. A., Venkataraman, A., Kulkarni, S. 2021


    The enteric nervous system (ENS) consists of an interconnected meshwork of neurons and glia residing within the wall of the gastrointestinal (GI) tract. While healthy GI function is associated with healthy ENS structure, defined by the normal distribution of neurons within ganglia of the ENS, a comprehensive understanding of normal neuronal distribution and ganglionic organization in the ENS is lacking. Current methodologies for manual enumeration of neurons parse only limited tissue regions and are prone to error, subjective bias, and peer-to-peer discordance. There is accordingly a need for robust, and objective tools that can capture and quantify enteric neurons within multiple ganglia over large areas of tissue. Here, we report on the development of an AI-driven tool, COUNTEN (COUNTing Enteric Neurons), which is capable of accurately identifying and enumerating immunolabeled enteric neurons, and objectively clustering them into ganglia. We tested and found that COUNTEN matches trained humans in its accuracy while taking a fraction of the time to complete the analyses. Finally, we use COUNTEN's accuracy and speed to identify and cluster thousands of ileal myenteric neurons into hundreds of ganglia thus computing metrics that help define the normal structure of the ileal myenteric plexus. To facilitate reproducible, robust, and objective measures of ENS structure across mouse models, experiments, and institutions, COUNTEN is freely and openly available to all researchers.Significance StatementCOUNTEN (COUNTing Enteric Neurons) is the first open-source AI-driven tool that performs automated, rapid, and objective enumeration and clustering of murine enteric neurons.

    View details for DOI 10.1523/ENEURO.0092-21.2021

    View details for PubMedID 34266963

  • Proprioception revisited: where do we stand? Current opinion in physiology Shadrach, J. L., Gomez-Frittelli, J., Kaltschmidt, J. A. 2021; 21: 23-28


    Originally referred to as 'muscle sense', the notion that skeletal muscle held a peripheral sensory function was first described early in the 19th century. Foundational experiments by Sherrington in the early 20th century definitively demonstrated that proprioceptors contained within skeletal muscle, tendons, and joints are innervated by sensory neurons and play an important role in the control of movement. In this review, we will highlight several recent advances in the ongoing effort to further define the molecular diversity underlying the proprioceptive sensorimotor system. Together, the work summarized here represents our current understanding of sensorimotor circuit formation during development and the mechanisms that regulate the integration of proprioceptive feedback into the spinal circuits that control locomotion in both normal and diseased states.

    View details for DOI 10.1016/j.cophys.2021.02.003

    View details for PubMedID 34222735

    View details for PubMedCentralID PMC8244174

  • Proprioception revisited: where do we stand? CURRENT OPINION IN PHYSIOLOGY Shadrach, J. L., Gomez-Frittelli, J., Kaltschmidt, J. A. 2021; 21: 23-28