Most fast excitatory postsynaptic potentials (fEPSPs) recorded from guinea
pig ileum myenteric plexus are mediated by acetylcholine acting at nicotini
c receptors and ATP acting at P2X receptors. These studies examine length a
nd polarity of projection of neurons releasing mediators of fEPSPs. Under k
etamine-xylazine anesthesia, animals were sham treated or myenteric pathway
s were interrupted. After severed axons degenerated, fEPSPs were recorded a
t the operated site using conventional, intracellular electrophysiological
methods and were classified as nicotinic or mixed on the basis of sensitivi
ty to hexamethonium. Cholinergic and noncholinergic fEPSPs were recorded fr
om small, operated segments, suggesting that some neurons have projections
between adjacent ganglia. The mean amplitudes of nicotinic and mixed fEPSPs
were reduced after circumferential and descending pathways degenerated. Th
e proportion of nicotinic vs. mixed fEPSPs recorded from tissues lacking de
scending projections was greater than that recorded from sham-treated tissu
es, suggesting that fibers releasing noncholinergic mediators project abora
lly. Descending projections communicate with neurons in ganglia at least th
ree rows aboral to their origin. The data suggest that fast noncholinergic
neurotransmission could contribute to hexamethonium-resistant descending in
hibition during the peristaltic reflex.