Electrophysiology of the human myenteric plexus

• Applicant: Professorin Gemma Mazzuoli-Weber, Ph.D.
• Subject Area: Gastroenterology ; Nutritional Sciences
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554130698

This project focuses on advancing our understanding of the human enteric nervous system (ENS), specifically the myenteric plexus, which plays a crucial role in regulating gastrointestinal motility. The ENS is often compared to an external hard disk controlling gastrointestinal functions and operating autonomously from the brain. Our literature research emphasizes the need for human-specific data, due to limitations in extrapolating findings from animal models to humans, as demonstrated by species-specific differences in neurotransmitter effects and signaling pathways. The present study proposes comprehensive research methods involving human intestinal (colonic) tissue sampling and preparation, neuroimaging with voltage and calcium-sensitive dyes, in vitro motility experiments in organ bath, and multi-layer immunohistochemistry. Our aim is to bridge the gap in knowledge regarding the functional properties and connectivity of human myenteric neurons. The experimental design involves investigating neuronal activation, neurotransmitter responses, and synaptic communication within the human colonic myenteric plexus. Additionally, the study aims to characterize and identify subclasses of enteric neurons by multiple staining immunohistochemistry, and to study spontaneous and nerve-mediated intestinal motility and its pharmacology. The project also aims to explore the influence of extrinsic afferents on intestinal motility. Furthermore, the project plans to assess the impact of patient characteristics especially in relation to age, sex, and body mass index on the neuronal count and motility data. In summary, the research project strives to provide a comprehensive understanding of the human colonic myenteric plexus, contributing valuable insights into the pathophysiology of functional gastrointestinal disorders and potentially paving the way for targeted therapeutic interventions.

• DFG Programme: Research Grants