Mechanosensitivity in the enteric nervous system: mechanotransduction and sensory circuitry

• Applicant: Professorin Gemma Mazzuoli-Weber, Ph.D.
• Subject Area: Gastroenterology ; Anatomy and Physiology
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 194394957

In the first three years of this project we successfully described and characterized multifunctional rapidly and slowly adapting mechanosensitive enteric neurons (RAMEN and SAMEN) in the stomach, small and large intestine of guinea pig, mouse and human. These neurons share common properties across regions and species, only their adaptation seems to be highly related to region-specific motility patterns. At a cellular level we showed that mechanosensitive enteric neurons have unique features that differ from other well-known sensory neurons, e.g. their soma is able to modulate incoming signals and they possess bidirectionally conducting neurites. The results were the basis for a PhD thesis, original publications, the research prize for Neurogastroenterology 2013 and last but not least the present project.For the next three years we will apply the well-established imaging techniques to achieve the following objectives. The first aim is to reveal the key elements of mechanotransduction in mechanosensitive enteric neurons by studying RAMEN- and SAMEN-specific involvement of ion channels or cytoskeleton modifications in encoding sensory signals. Moreover, the results may identify targets to treat sensory-motor disorders. The second aim is to identify and characterize the so far unknown properties of mechanosensitive neurons in the submucous plexus which, based on functional studies, indeed regulates reflex driven mucosal secretion. The third aim is to clarify the functional role of RAMEN and SAMEN in the gut reflex motor activity. To achieve this we will map signal spread between myenteric ganglia after mechanical stimulation in order to record activity of neurons that are part of a sensory-motor circuit.It is expected that the results will reveal novel features of mechanosensitive enteric circuits important for advancements of both basic and translational neurogastroenterology.

• DFG Programme: Research Grants