Computer simulation of the enteric neural circuits mediating an ascending reflex: Roles of fast and slow excitatory outputs of sensory neurons

doi:10.1016/S0165-1838(97)00027-1

Journal of the Autonomic Nervous System

Volume 64, Issues 2–3, 6 June 1997, Pages 143-157

Journal of the Auton...

https://doi.org/10.1016/S0165-1838(97)00027-1 Get rights and content

Abstract

Recent electrophysiological studies of the properties of intestinal reflexes and the neurons that mediate them indicate that the intrinsic sensory neurons may transmit to second order neurons via either fast (30–50 ms duration) or slow (10–60 s duration) excitatory synaptic potentials or both. Which of these possible modes of transmission is involved in the initiation of motility reflexes has not been determined and it is not clear what the consequences of the different forms of synaptic transmission would be for the properties of the reflex pathways. In the present study, this question has been addressed by the use of a suite of computer programs, Plexus©, which was written to simulate the activity of the neurons of the enteric nervous system during intestinal reflexes. The programs construct a simulated enteric nerve circuit based on anatomical and physiological data about the number, functions and interconnections of neurons involved in the control of motility. The membrane potentials of neurons are calculated individually from physiological data about the reversal potentials and membrane conductances for Na⁺, K⁺ and Cl⁻. Synaptic potentials are simulated by changes in specific conductances based on physiological data. The results of each simulation are monitored by recording the membrane potentials of up to 16 separate defined neurons and by recording the summed activity of whole classes of neurons as a function of time and location in the simulated network. The present series of experiments simulated the behaviour of a network consisting of 18 898 sensory neurons and 3708 ascending interneurons after 75% of the sensory neurons lying in the anal 10 mm of a 30 mm long segment of small intestine were stimulated once. The results were compared with electrophysiological data recorded from myenteric neurons during ascending reflexes evoked either by distension or mechanical stimulation of the mucosa. When transmission from sensory neurons to ascending interneurons was via fast excitatory synaptic potentials, the latencies and durations of the simulated responses were too brief to match the electrophysiologically recorded responses. When transmission from sensory neurons was via slow excitatory synaptic potentials, the latencies were very similar to those recorded physiologically, but the durations of the simulated responses were much longer than seen in physiological experiments. The latencies and durations of simulated and physiologically recorded responses matched only when the firing of ascending interneurons was limited to the beginning of a slow excitatory synaptic potential (in this study by limiting the duration of the decrease in K⁺ conductance). The simulation provided several physiologically testable predictions, indicating that Plexus© is an important tool for the investigation of the properties and behaviour of the enteric nervous system.

Section snippets

Background

The behaviour of the intestine depends on the coordinated activity of its vast population of intrinsic neurons, the enteric nervous system. Enteric neurons mediate distinct behaviours, including mixing and propulsion of intestinal content and the migrating complexes commonly seen when an animal is fasting. Both propulsion and the migrating complexes have been the subjects of extensive physiological analyses; however, while propulsion is now reasonably well characterised, the neural circuitry

Anatomy

A suite of programs (Plexus©) has been written which constructs an anatomically realistic myenteric plexus from rules set down by the operator and then can simulate the activity of the plexus. To begin the process, the number of neurons per square centimetre, the number and distribution of neurons per ganglion and the length and circumference of the segment of intestine to be modelled are specified. The program then calculates the number of ganglia in the intestinal segment and distributes them

Experimental protocols

The experiments began by defining a suitable segment of intestine and extracting an appropriate subnetwork. Once this was done, the number (18 898 sensory and 3708 ascending interneurons) and distribution of neurons and the connections they made was not varied for the remainder of the study. Similarly, reversal potentials for the various ionic conductances and the amplitudes of the sodium conductance changes underlying action potentials were left unaltered throughout the study.

Other parameters

Initial qualitative observations

Activation of sensory neurons in the anal third of the simulated preparation evoked an orally propagating wave of excitation in the ascending interneurons whether the output of sensory neurons was assumed to be via fast or slow EPSPs (Fig. 7Fig. 8). In each case, the response of ascending interneurons lying outside the stimulus region was a burst of fast EPSPs, some of which exceeded threshold for initiation of an action potential either because of their own amplitude or because of summation.

Discussion

The results illustrated here indicate that Plexus© can simulate many of the properties of the ascending reflex pathway in the guinea-pig small intestine. Indeed, use of the model provides some interesting, and physiologically testable, predictions about the normal physiology of the reflex pathways.

One of the major comparisons made in the current series of simulations has been between different forms of output from the sensory neurons to their target interneurons in the ascending pathway. The

Acknowledgements

This work was supported by a Program Grant (No. 963213) from the National Health and Medical Research Council of Australia. Mr. E.A. Thomas and Dr. W.A.A. Kunze are thanked for their valuable comments on the manuscript. The source code for the latest version of Plexus (include copyright symbol) and an instruction manual can be obtained via our laboratory home page URL: <http://plexus.physiol.unimelb.edu.au/ang/ang.htm>

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¹: Present address: QED Research Unit, Monash University, Clayton, Vic 3168, Australia.

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Computer simulation of the enteric neural circuits mediating an ascending reflex: Roles of fast and slow excitatory outputs of sensory neurons

Abstract

Section snippets

Background

Anatomy

Experimental protocols

Initial qualitative observations

Discussion

Acknowledgements

J. Auton. Nerv. Syst.

Neuroscience

Neuroscience

J. Auton. Nerv. Syst.

Neuroscience

Neuroscience

Neuroscience

Contribution of chloride conductance increase to slow EPSC and tachykinin current in guinea-pig myenteric neurones

J. Physiol.

Local neural control of intestinal motility: Nerve circuits deduced for the guinea-pig small intestine

Clin. Exp. Pharmacol. Physiol.

Electrophysiology and enkephalin immunoreactivity of identified myenteric plexus neurones in the guinea-pig small intestine

J. Physiol.

Synaptic responses evoked by mechanical stimulation of the mucosa in morphologically characterized myenteric neurons of the guinea pig ileum

J. Neurosci.

Ramifications of the axons of AH-neurons injected with the intracellular marker biocytin in the myenteric plexus of the guinea pig small intestine

J. Comp. Neurol.

Calretinin immunoreactivity in cholinergic motor neurones, interneurones and vasomotor neurones in the guinea-pig small intestine

Cell Tissue Res.

Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone

J. Physiol.

The circuitry of the enteric nervous system

Neurogastroenterol. Mot.