Coordination of intrinsic neural network connectivity in the gut by enteric glial DISC1 (R-10587)

The neurons and glia of the enteric nervous system, the little brain that regulates digestive function, form a carefully wired network in the wall of the gut. Our previous studies have shown that specific spatial positioning of enteric neurons and glia and the orientation of their processes are fundamental for the layout of mature enteric networks. However, it is not clear how the neural circuits that control gut motility and secretion are put together. Insight into the mechanisms that control wiring of the second brain is important to improve understanding of digestive diseases believed to arise from erroneous enteric neural circuits. Moreover, abnormal enteric neural circuits that lead to changes in intestinal motility could imbalance the intestinal microbiome and affect brain function via the gut-brain axis. We hypothesize that enteric glial cells are crucially important for the formation and maintenance of those circuits, and that disturbed glial function through perturbation of the major mental illness risk factor DISC1 causes faulty enteric neuron wiring. We will elucidate how enteric glial cells, through DISC1 signaling, are involved in enteric neuron connectivity, gut function and intestinal homeostasis. Our approach, which combines innovative genetic and neurophysiological tools with cutting-edge live cell microscopy, provides powerful means to unravel enteric neuron circuits and the role of enteric glial cells in their assembly.

Keywords:Electrophysiology, Enteric Nervous system, neurogastroenterology

Disciplines:Gastro-enterology, Neurophysiology