▪ Abstract Brainstem parasympathetic circuits that modulate digestive functions of the stomach are comprised of afferent vagal fibers, neurons of the nucleus tractus solitarius (NTS), and the efferent fibers originating in the dorsal motor nucleus of the vagus (DMV). A large body of evidence has shown that neuronal communications between the NTS and the DMV are plastic and are regulated by the presence of a variety of neurotransmitters and circulating hormones as well as the presence, or absence, of afferent input to the NTS. These data suggest that descending central nervous system inputs as well as hormonal and afferent feedback resulting from the digestive process can powerfully regulate vago-vagal reflex sensitivity. This paper first reviews the essential “static” organization and function of vago-vagal gastric control neurocircuitry. We then present data on the opioidergic modulation of NTS connections with the DMV as an example of the “gating” of these reflexes, i.e., how neurotransmitters, hormones, and vagal afferent traffic can make an otherwise static autonomic reflex highly plastic.

Vagal neurocircuits are vitally important in the co-ordination and modulation of GI reflexes and homeostatic functions. 5-hydroxytryptamine (5-HT; serotonin) is critically important in the regulation of several of these autonomic gastrointestinal (GI) functions including motility, secretion and visceral sensitivity. While several 5-HT receptors are involved in these physiological responses, the ligand-gated 5-HT3 receptor appears intimately involved in gut-brain signaling, particularly via the afferent (sensory) vagus nerve. 5-HT is released from enterochromaffin cells in response to mechanical or chemical stimulation of the GI tract which leads to activation of 5-HT3 receptors on the terminals of vagal afferents. 5-HT3 receptors are also present on the soma of vagal afferent neurons, including GI vagal afferent neurons, where they can be activated by circulating 5-HT. The central terminals of vagal afferents also exhibit 5-HT3 receptors that function to increase glutamatergic synaptic transmission to second order neurons of the nucleus tractus solitarius within the brainstem. Thus, activation of 5-HT3 receptors may modulate the excitability and activity of gastrointestinal vagal afferents at multiple sites and may be involved in several physiological and pathophysiological conditions, including distention- and chemical-evoked vagal reflexes, nausea and vomiting, as well as visceral hypersensitivity

1 The electrophysiological properties of rat dorsal motor nucleus of the vagus (DMV) neurones (n= 162) were examined using whole cell patch clamp recordings from brainstem slices. Recordings were made from DMV neurones whose projections to the gastrointestinal tract had been identified by previously applying fluorescent retrograde tracers to the gastric fundus, corpus or antrum/pylorus, or to the duodenum or caecum. 2 The neuronal groups were markedly heterogeneous with respect to several electrophysiological properties. For example, neurones which projected to the fundus had a higher input resistance (400 ± 25 MΩ), a smaller and shorter after-hyperpolarization (16.7 ± 0.49 mV and 63.5 ± 3.9 ms) and a higher frequency of action potential firing (19.3 ± 1.4 action potentials s⁻¹) following injection of depolarizing current (270 pA) when compared with caecum-projecting neurones (302 ± 22 MΩ; 23.5 ± 0.87 mV and 81.1 ± 5.3 ms; 9.7 ± 1.1 action potentials s⁻¹; P < 0.05 for each parameter). Differences between neuronal groups were also apparent with respect to the distribution of several voltage-dependent potassium currents. Inward rectification was present only in caecum-projecting neurones, for example. 3 Neurones (n= 82) were filled with the intracellular stain Neurobiotin allowing post-fixation morphological reconstruction. Neurones projecting to the caecum had the largest cell volume (5238 ± 535 μm³), soma area (489 ± 46 μm²) and soma diameter (24.6 ± 1.24 μm) as well as the largest number of dendritic branch segments (23 ± 2). 4 In summary, these results suggest that DMV neurones are heterogeneous with respect to some electrophysiological as well as some morphological properties and can be divided into subgroups according to their gastrointestinal projections.