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Am J Physiol Gastrointest Liver Physiol (January 6, 2005). doi:10.1152/ajpgi.00491.2004
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Submitted on October 29, 2004
Accepted on December 23, 2004

Recurrent networks of submucous neurons controlling intestinal secretion: a modelling study

Jordan D. Chambers1*, Joel C. Bornstein1, Henrik Sjovall2, and Evan A. Thomas3

1 Department of Physiology, University of Melbourne, Parkville, Vic, Australia
2 Department of Internal Medicine, Sahlgrenska University Hospital, Goteborg, Sweden
3 Department of Physiology, University of Melbourne, Parkville, Vic, Australia; Howard Florey Institute, Parkville, Vic, Australia

* To whom correspondence should be addressed. E-mail: jordanc{at}unimelb.edu.au.

Secretomotor neurons, immunoreactive for vasoactive intestinal peptide (VIP), are important in controlling chloride secretion in the small intestine. These neurons form functional synapses with other submucosal VIP neurons and transmit via slow excitatory post-synaptic potentials (EPSPs). Thus, they form a recurrent network with positive feedback. Intrinsic sensory neurons within the submucosa are also likely to form recurrent networks with positive feedback, provide substantial output to VIP neurons and receive input from VIP neurons. If positive feedback within recurrent networks is sufficiently large, then neurons in the network respond to even small stimuli by firing at their maximum possible rate, even after the stimulus is removed. However, it is not clear whether such a mechanism operates within the recurrent networks of submucous neurons. We investigated this question by performing computer simulations of realistic models of VIP and intrinsic sensory neuron networks. In the expected range of electrophysiological properties we found that activity in the VIP neuron network decayed slowly after cessation of a stimulus, indicating that positive feedback is not strong enough to support the uncontrolled firing state. The addition of intrinsic sensory neurons produced a low stable firing rate, which is consistent with the common finding that basal secretory activity is in part neurogenic. Changing electrophysiological properties enables these recurrent networks to support the uncontrolled firing state, which may have implications with hypersecretion in the presence of enterotoxins such as cholera-toxin.




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