ABSTRACT

The enteric nervous system plays a central role in the control of gastrointestinal function. To understand how its circuits operate, it is necessary to identify and characterise the different functional classes of enteric neurones and determine their cellular properties and connectivity. The most powerful way to distinguish the different classes of neurones has been to study the combinations of neurochemicals (“chemical coding”) that they contain in their cell bodies and axons. Some of the neurochemicals in the chemical codes, such as neurotransmitters, may be functionally important in their own right. The role of other molecules, such as calcium binding proteins, are currently unclear, however they are still useful as markers to distinguish various classes of neurones. In combination with axonal tracing techniques, chemical coding has provided a quantitative account of all of the major classes of neurones in one preparation, the guinea-pig ileum. Extensive electrophysiological and morphological studies have been readily incorporated into this account. This has revealed an exquisite degree of organisation, comparable to many parts of the central nervous system. Each class of neurone has characteristic combinations of neurotransmitters, neuromodulators, synaptic inputs, projections and soma-dendritic morphology. The methodologies developed in the guinea-pig small intestine are increasingly being applied to other regions of gastrointestinal tract and to preparations from other species. While many characteristics appear to be shared by different preparations, substantial differences are beginning to emerge, even between neurones with apparently identical functions. It is clear that the guinea-pig ileum is not representative of the enteric nervous system in general, nor of the human enteric nervous system in particular. However, neither is any other animal model. Fortunately, with the techniques now available, it is possible to study directly specimens of human gut, reducing the reliance on animal models to answer fundamental questions of the cellular organisation of the human enteric nervous system. Changes in the chemical coding during development and in diseases will cast light onto both the mechanisms underlying plasticity of the enteric nervous system and the processes underlying physiopathological changes.