SUBPOPULATIONS OF GASTRIC MYENTERIC NEURONS ARE DIFFERENTIALLY ACTIVATED VIA DISTINCT SEROTONIN RECEPTORS - PROJECTION, NEUROCHEMICAL CODING, AND FUNCTIONAL IMPLICATIONS

The enteric nervous system coordinates various gut functions. Function al studies suggested that neurotransmitters and neuromodulators, one o f the most prominent among them being 5-HT, may act through a specific modulation of ascending and descending enteric pathways. However, it is still mostly unknown how particular components of enteric reflex ci rcuits are controlled. This report describes experiments aimed at iden tifying a differential activation of enteric pathways by 5-HT. Electro physiological and immunohistochemical methods were combined to investi gate the projection pattern and the transmitter phenotype of 5-HT-sens itive gastric myenteric neurons. Of 294 intracellularly labeled neuron s, 60.5% showed responses mediated via 5-HT3 receptors, 11.3% were 5-H T1P-responsive, 3.7% exhibited both 5-HT3 and 5-HT1P receptor-mediated depolarization, and 24.5% were not responding to 5-HT. The 5-HT3-resp onsive cells were mainly cholinergic (79%) and had ascending projectio ns, whereas the 5-HT1P-responsive cells had primarily descending proje ctions and were nitrergic (67%). Substance P-positive neurons were cho linergic; most of the cells (75%) exhibited 5-HT3 mediated responses a nd had ascending projections. Muscle strip recordings supported the fu nctional significance of the differential location of 5-HT receptor su btypes. Thus, contractile responses of gastric circular muscle strips were dose-dependently increased by a 5-HT3 and decreased by a 5-HT1P a gonist. Results indicated that excitatory ascending enteric pathways c onsisting of cholinergic, substance Pergic neurons were activated by 5 -HT3 receptors, whereas 5-HT1P receptors were involved in activation o f inhibitory descending pathways using nitrergic neurons. This suggest ed that different effects of 5-HT on gastric functions are related to specific activation of receptors located on different subsets of enter ic neurons.