Insights into intestinal fed-state motor patterns

© 2010 Dr. Jordan David ChambersAfter a meal, the duodenum and jejunum exhibit a specific set of contractile patterns, collectively known as the fed-state, which facilitate the functions of the gastrointestinal tract. Non-propagating contractions observed during the fed-state are known as segmentation. In the guinea pig small intestine, nutrient induced motor activity consists of a number of discrete motor patterns including propulsive contractions and rhythmic stationary contractions (segmentation) that occur episodically at specific locations along the intestine. In addition to rhythmic stationary contractions, during segmentation episodes of activity incorporating all contractions last 40-60s and are separated by quiescent periods lasting 40-200s. The enteric nervous system (ENS) regulates segmentation, but the exact circuit is unknown. Possible circuits were investigated using a combination of computer models and video recordings of segmentation in vitro using guinea-pig jejunum, in which segmentation was induced with luminal fatty acid. A simple computer model simulated the mean neuron firing rate in the feedforward ascending and descending reflex pathways. A stimulus evoked pacemaker was located in the afferent pathway or in a feedforward pathway. Output of the feedforward pathways was fed into a simple model to determine the response of the muscle. In this computational model, local stimuli produced an oral contraction and anal dilation, similar to in vitro responses to local distension, but did not produce segmentation. When the stimulus was distributed, representing a nutrient load, the result was either a tonic response or globally synchronized oscillations. However, when local variations were introduced, stationary contractions occurred around these locations. This predicts that severing the ascending and descending pathways will induce stationary contractions. An acute lesion of the longitudinal muscle, myenteric plexus and circular muscle around the entire circumference of the intestine significantly increased the number of stationary contractions immediately oral and anal to the lesion in vitro. These results suggest spatially localised rhythmic contractions arise from a local imbalance between ascending excitatory and descending inhibitory muscle inputs. Also, these results require a distributed stimulus and a rhythm generator in the afferent pathway. A possible rhythm generator in the afferent pathway was targeted pharmacologically by blocking after-hyperpolarising potentials (AHPs) in sensory neurons in vitro. Blocking AHPs did not affect properties of rhythmic stationary contractions, but increased the duration of activity episodes without affecting quiescent periods. This indicates that there are at least two separate rhythm generators operating concurrently during segmentation, which determine the rhythms of stationary contraction and episodes of activity. A computer model was developed to explain the changes in activity episodes without affecting the quiescent periods. The model described activity in sensory neurons, excitatory and inhibitory motor neurons, and feedback to sensory neurons. The model could reproduce the pharmacological data provided there was feedback to sensory neurons via contraction induced serotonin release. It also required fast transmission from sensory neurons to excitatory motor neurons and slow transmission from sensory neurons to inhibitory motor neurons. Therefore, the model identified plausible functions for known mechanisms and predicted relative strength of synaptic transmission in the ENS