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1. Electrophysiological recordings were made from neurones in the submucous plexus of the guinea-pig small intestine, and these neurones were classified according to their synaptic inputs. 2. The neurones from which recording were made were filled during the recording period with the fluorescent dye, Lucifer Yellow, so they could be re-identified after processing for immunohistochemical localization of vasoactive intestinal peptide (VIP). 3. The presence or absence of VIP-like immunoreactivity was determined for a total of 130 neurones whose synaptic inputs had been fully characterized and eighty-two were found to be VIP reactive. After the VIP reactivity had been assessed, the preparations were reprocessed to reveal immunoreactivity for neuropeptide Y (NPY) and a further twenty-three neurones (none of which were reactive for VIP) were found to be reactive for this peptide. Of the remaining twenty-five neurones, nineteen were not reactive for either VIP or NPY and six could not be re-identified after reprocessing. 4. Electrical stimulation of internodal strands evoked excitatory synaptic potentials lasting 20-30 ms (fast responses) in all but one of the 130 neurones studied. 5. Almost all the VIP-reactive neurones (seventy-eight of eighty-two cells) exhibited inhibitory synaptic potentials, ranging in amplitude from 2 to 30 mV and lasting 150-1500 ms, but few of the VIP-negative neurones had such responses (six of forty-eight cells). No inhibitory synaptic potentials could be evoked in any of the NPY-reactive neurones. 6. Most VIP-reactive neurones (sixty-nine) had a slow excitatory synaptic potential which could be evoked by a single stimulus, lasted 5-20 s and was associated with an increase in input resistance. Only one NPY-reactive neurone had a slow excitatory potential, but such potentials were seen in nine of the nineteen VIP-negative, NPY-negative neurones. 7. In nine of the twenty-three NPY-reactive neurones a single stimulus evoked an excitatory synaptic potential (intermediate excitatory synaptic potential) lasting 500-1500 ms and associated with a fall in the input resistance. None of the VIP-negative, NPY-negative neurones exhibited the intermediate excitatory potentials but it was not possible to determine whether such potentials could be evoked in VIP-reactive neurones because the inhibitory synaptic potentials would obscure such events. 8. It is concluded that neurochemically distinct populations of submucous neurones can be distinguished physiologically on the basis of the differing combinations of types of synaptic input they receive.
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