Correlated electrophysiological and histochemical studies of submucous neurons and their contribution to understanding enteric neural circuits

Abstract

Neither submucous ganglia, nor intestinal secretomotor reflexes are mentioned in the majority of the textbooks of physiology; because it has been realized only very recently that the submucous neurons may have important influences on whole body water and electrolyte balance. In the present review, we trace the rapid progress that has been made in determining the physiological properties of submucous neurons with known chemistry and projections in the guinea-pig small intestine, and we analyze how the work relates to studies in vivo of the neuronal control of intestinal trans-epithelial fluid transport. Four types of submucous neurons, which appear to be the full complement in the guinea-pig small intestine, have been identified through electrophysiological and histochemical analysis. (1) Cholinergic secretomotor neurons contain immunoreactivity for choline-acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY), somatostatin (SOM), and in the majority of cases galanin (GAL); these neurons project to the mucosal epithelium. (2) Non-cholinergic secretomotor neurons contain dynorphin (DYN), GAL and vasoactive intestinal peptide (VIP); these neurons project to the mucosa and provide collaterals to submucous arterioles. (3) Cholinergic interneurons contain ChAT alone; these neurons connect with the secretomotor neurons. (4) Presumed sensory neurons contain ChAT and substance P (SP) and have nerve endings in the mucosa. The two groups of secretomotor neurons receive cholinergic synaptic inputs from both myenteric and submucous ganglia. In addition, the DYN/GAL/VIP neurons receive sympathetic inhibitory inputs as well as inhibitory and non-cholinergic excitatory inputs from myenteric ganglia. The ChAT/SP nerve cells in submucous ganglia receive no or very ineffective inputs. From these data, from experiments on transmission from the neurons to the intestinal epithelium, and from studies of secretomotor reflexes in vivo, a correlated functional and structural circuitry of the submucous ganglia and their connections has been deduced. It is concluded that secretomotor reflexes are stimulated by the contents of the lumen during the digestion and absorption of food and that these reflexes cause a proportion of water and electrolytes that are absorbed with nutrients such as glucose to be returned to the lumen. The balance of absorption and secretion of water and electrolytes is controlled by sympathetic inhibitory inputs to secretomotor neurons, the activity in sympathetic pathways being varied to contribute to whole body water and electrolyte balance.