The enteric nervous system is a specialised part of the autonomic nervous system that contains full reflex circuits (intrinsic sensory neurons, interneurons and motor neurons that integrate information about the state of the intestine and provide suitable outputs). It can thus operate independently of the CNS, but under normal circumstances the ENS and CNS act co-operatively in digestive system control. The ENS contains a very large number of neurons, around 400 million in human, belonging to around 17 functional types. The circuits for enteric reflex control have been largely worked out, and all the neuron types have been accounted for. This work will be summarised. 　

Knowledge of the circuitry and neuron types provides a sound basis for investigation of animal models of enteric neuropathies and for identifying possible neuronal target molecules for therapies. In this presentation, I will discuss the enteric neuron changes that follow inflammation in animal models. These parallel changes observed in human (post-inflammatory irritable bowel syndrome, IBS). The remarkable change seen in models of IBS is the profound hyperexcitability of intrinsic sensory neurons (known as intrinsic primary afferent neurons, or IPANs). This hyperexcitability substantially outlasts the period of inflammatory damage - it is a neuropathy. I will discuss another type of damage that is under investigation, the damage that accompanies ischemia/ reperfusion injury to the intestine. 　

If damage to neurons is irreversible, is it possible to replace the enteric neurons, using neural stem cells? I will describe experiments in which we have prepared neurospheres from the intestine and have transplanted them into normal and enteric neuron deficient colon. The transplanted neuron precursors proliferate, migrate, differentiate and innervate targets.