Recurrent networks of submucous neurons controlling intestinal secretion: a modeling study.
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 postsynaptic 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 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.
Chambers
Jordan D
JD
Deptartment of Physiology, University of Melbourne, Parkville Victoria 3010, Australia. jordanc@unimelb.edu.au
Bornstein
Joel C
JC
Sjövall
Henrik
H
Thomas
Evan A
EA
D000200:Action Potentials; D000818:Animals; D003198:Computer Simulation; D019706:Excitatory Postsynaptic Potentials; D007413:Intestinal Mucosa / Q000294:innervation*; D007419:Intestinal Secretions / Q000502:physiology*; D008959:Models, Neurological; D009415:Nerve Net; D009474:Neurons / Q000502:physiology*