Enteric neural circuits underlying propulsion of content in the large intestine of mammals

Author: David Smolilo

Smolilo, David, 2021 Enteric neural circuits underlying propulsion of content in the large intestine of mammals, Flinders University, College of Medicine and Public Health

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The enteric nervous system (ENS) plays a central role in mammalian gut physiology and is essential for normal function. Individual nerve cells contribute to the formation of complex functional circuits; their projections travel within and across the layers of the gut wall to form close associations with other neurons, smooth muscle cells and cells of the immune and endocrine systems. The circuits of the ENS take part in the initiation and control of gut motor patterns, they influence mucosal secretion, blood vessel tone and function of neuro-endocrine cells. They provide sensory feedback to the central nervous system and in turn are influenced by input from spinal efferent nerves. Over the last few decades, multiple distinct populations of ENS nerve cells have been described according to characteristics such as morphology, electrophysiology and immunoreactive content. However, our understanding of how these neurons are connected, to form physical and functional circuits, is far from complete. The work presented in this thesis advances the detailed knowledge of connectivity of distinct neural circuits in the enteric nervous system of the mammalian colon.

Chapter 1 is a review of current literature relevant to this project. In Chapter 2, we describe a novel circuit that involves the intrinsic sensory neurons of the gut preferentially directing their synaptic output onto populations of calretinin-containing neurons within the myenteric plexus of the guinea pig colon. We expand on this finding in Chapter 3, where neuronal tracing confirms our initial hypotheses and expands on previous knowledge of neuronal projections in the colon.

Chapter 4 explores the connectivity of intrinsic sensory neurons using immunohistochemistry and tissue culture in the mouse colon. Given the advancing genetic manipulation techniques in this animal, it is of great interest to understand the connectivity within its ENS more fully and compare with already described systems.

Studies that examine neural connectivity within the ENS provide the basis for understanding functional observations and guide further experiments. Correlating neural circuits with function helps to translate experimental data into a broader understanding of gut physiology, and sets up a foundation for the development of possible interventions in gut pathology.

Keywords: Enteric nervous system, intrinsic primary afferent neurons, calbindin, calretinin, neuroanatomy

Subject: Medical Science thesis

Thesis type: Doctor of Philosophy
Completed: 2021
School: College of Medicine and Public Health
Supervisor: Professor Nicholas Spencer