Intrinsic primary afferent neuronsof the intestine

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Abstract

After a long period of inconclusive observations, the intrinsic primary afferent neurons of the intestine have been identified. The intestine is thus equipped with two groups of afferent neurons, those with cell bodies in cranial and dorsal root ganglia, and these recently identified afferent neurons with cell bodies in the wall of the intestine.

The first, tentative, identification of intrinsic primary afferent neurons was by their morphology, which is type II in the terminology of Dogiel. These are multipolar neurons, with some axons that project to other nerve cells in the intestine and other axons that project to the mucosa.

Definitive identification came only recently when action potentials were recorded intracellularly from Dogiel type II neurons in response to chemicals applied to the lumenal surface of the intestine and in response to tension in the muscle. These action potentials persisted after all synaptic transmission was blocked, proving the Dogiel type II neurons to be primary afferent neurons.

Less direct evidence indicates that intrinsic primary afferent neurons that respond to mechanical stimulation of the mucosal lining are also Dogiel type II neurons.

Electrophysiologically, the Dogiel type II neurons are referred to as AH neurons. They exhibit broad action potentials that are followed by early and late afterhyperpolarizing potentials.

The intrinsic primary afferent neurons connect with each other at synapses where they transmit via slow excitatory postsynaptic potentials, that last for tens of seconds. Thus the intrinsic primary afferent neurons form self-reinforcing networks.

The slow excitatory postsynaptic potentials counteract the late afterhyperpolarizing potentials, thereby increasing the period during which the cells can fire action potentials at high rates.

Intrinsic primary afferent neurons transmit to second order neurons (interneurons and motor neurons) via both slow and fast excitatory postsynaptic potentials.

Excitation of the intrinsic primary afferent neurons by lumenal chemicals or mechanical stimulation of the mucosa appears to be indirect, via the release of active compounds from endocrine cells in the epithelium. Stretch-induced activation of the intrinsic primary afferent neurons is at least partly dependent on tension generation in smooth muscle, that is itself sensitive to stretch.

The intrinsic primary afferent neurons of the intestine are the only vertebrate primary afferent neurons so far identified with cell bodies in a peripheral organ. They are multipolar and receive synapses on their cell bodies, unlike cranial and spinal primary afferent neurons. They communicate with each other via slow excitatory synaptic potentials in self reinforcing networks and with interneurons and motor neurons via both fast and slow EPSPs.

Section snippets

The enteric nervous system and intrinsic intestinal reflexes

This review describes the properties of recently identified primary afferent neurons that have cell bodies within the wall of the gastrointestinal tract. These neurons are referred to as intrinsic primary afferent neurons, to differentiate them from the spinal and vagal primary afferent neurons that innervate the gastrointestinal tract (Fig. 1). They have a morphology that is referred to as Dogiel type II and belong to an electrophysiological class known as AH neurons.

The enteric nervous

Identification of Dogiel type II neurons as intrinsic primary afferent neurons

Considerations of their morphology led Dogiel (1899)to suggest that the type II neurons might be intrinsic primary afferent neurons. Dogiel traced processes (which he called dendrites) from these nerve cells to the mucosa and processes he called axons to other ganglia; he deduced that the projections to the mucosa were sensory and the projections in the ganglia provided outputs to other neurons. In a slightly later morphological study, Kuntz (1913)came to the same conclusion. He identified

Electrophysiological properties of AH/Dogiel type II neurons

The electrophysiological properties of the Dogiel type II neurons are influenced by the recording conditions, which can determine whether the intrinsic primary afferent neurons are active and whether there is ongoing synaptic transmission that affects their properties. Under conditions in which spontaneous activity of neurons and, therefore, background synaptic transmission are suppressed, they exhibit properties that identify them as AH neurons in the terminology of Hirst et al. (1974). In

Relation of recent findings to earlier observations

The first experiments in which recordings were made directly from intrinsic primary afferent neurons appear to be those of Wood (1970)and Wood (1973). In these experiments, records were taken from myenteric ganglia with extracellular electrodes pressed against the ganglion surface. Action potentials were recorded from a population of neurons referred to as phasic mechanoreceptors in the initial work, but referred to later as slowly adapting mechanoreceptors (Wood, 1975, Wood, 1994). The slowly

Intrinsic primary afferent neurons have characteristics that differentiate them from other mammalian primary afferent neurons

Both the morphology and the physiological characteristics of the intrinsic primary afferent neurons have some unusual features, when compared with the historically more thoroughly studied primary afferent neurons with cell bodies in cranial or spinal (dorsal root) ganglia (Fig. 1; Fig. 9). An obvious difference is that the majority of the intrinsic primary afferent neurons are multipolar, whereas neurons of the cranial and spinal ganglia are pseudounipolar. Action potentials that arise in one

Acknowledgements

The authors' studies reported in this review were supported by the National Health and Medical Research Council of Australia (grant 963213). Dr Paul Bertrand held a National Institutes of Health (NIDDK) Research Training Fellowship, # DK 09162 (USA). Dr Nadine Clerc was a Visiting Research Fellow of the University of Melbourne, on leave from the Centre National de la Recherche Scientifique, France. We thank Siobhan Lavin and Heather Woodman for excellent assistance with the illustrations and

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