Journal of Neuroscience, Vol 10, 1025-1034, Copyright © 1990 by Society for Neuroscience
A vasoactive intestinal peptide-like cotransmitter at cholinergic synapses between rat myenteric neurons in cell culture
AL Willard
Department of Physiology, University of North Carolina, Chapel Hill 27599.
Intracellular recording and immunochemical techniques were used to study
synaptic transmission between individual pairs of rat myenteric plexus
neurons in cell culture. This report describes the synaptic connections
made by "dual function" presynaptic neurons that evoked slow postsynaptic
depolarizations (slow EPSPs) in the same neurons in which they also evoked
fast nicotinic cholinergic EPSPs. The slow EPSPs occurred only when
presynaptic neurons were stimulated at frequencies of 5 Hz or higher.
During the slow EPSPs, slope input resistance increased. The slow EPSPs
were not detectably voltage-dependent, and they reversed sign at the
estimated K+ equilibrium potential, suggesting that they resulted from a
synaptically mediated decrease in resting K+ conductance. Several lines of
evidence suggested that dual- function neurons evoke slow EPSPs by
releasing a vasoactive intestinal peptide (VIP)-like cotransmitter. (1)
Immunocytochemical staining revealed VIP-like immunoreactivity in all
physiologically identified dual-function neurons. (2) Responses to
exogenously applied VIP mimicked the slow EPSPs. (3) Superfusion of
cultures with anti-VIP antisera blocked the slow EPSPs reversibly, as did
application of desensitizing doses of VIP. These findings suggest that
during periods of increased activity, subsets of cholinergic myenteric
neurons release a VIP-like cotransmitter that enhances postsynaptic
excitability. The effects of the cotransmitter may help to compensate for
decreases in nicotinic EPSPs that occur during increased presynaptic
activity.