We are interested in the interplay between classical neurotransmitters and neuropeptides in the control of behaviour. To investigate this we have used electrophysiological recordings from C. elegans pharynx and determined the actions of putative neurotransmitters and neuromodulators on muscle activity. To date, we have only found two agents which inhibit the frequency of pharyngeal action potentials without having any significant effect on basal resting membrane potential, namely octopamine (Franks et al., 1998) and a peptide encoded by the gene
flp-3 (SAEPFGTMRFamide: FLP-3). Their action may be described as switching the pharynx off. Neither octopamine nor FLP-3 seem to be present in neurones directly impinging on the pharynx (e.g. Alkema & Horvitz, 1999; Kim & Li, 1999) and therefore their actions are likely to be indirect and involve neurotransmitter release from other neurones. We tested this by comparing the actions of octopamine and FLP-3 between wild-type and a mutant with a severe deficit in synaptic transmission,
snb-1 . Pharyngeal action potential frequency was measured by intracellular recordings from the terminal bulb. Activity was stimulated at a constant rate by the addition of 500 nM 5-HT to the perfusate and the spike rate then determined upon addition of either octopamine or FLP-3. Both octopamine and FLP-3 caused a more potent inhibition in
snb-1 compared to wild-type. This may be explained if octopamine and FLP-3 exert their inhibitory action by inhibiting release of an excitatory transmitter. Therefore, in a mutant with impaired neurotransmission, such as
snb-1, this inhibition of release may be achieved at lower concentrations of the modulator. In the motonervous system it has been shown that the inhibition of release of the excitatory transmitter, ACh, by 5-HT is mediated through the G-protein, GOA-1 (Segalat et al., 1995; Nurrish et al., 1999), and this would also appear to be the case in the pharyngeal nervous system, as both FLP-3 and octopamine are less effective in the mutant
goa-1. We are now considering whether the switch that both octopamine and FLP-3 control is the cholinergic pharnygeal motoneurone MC. Alkema & Horvitz, 1999 International Worm Meeting Abstract 148 Franks, Chad, Walker & Holden-Dye 1998 European Worm Meeting Abstract
t40 Kim & Li, 1999 Soc Neurosci Abs. 69.1 Nonet, Saifee, Zhou, Rand & Wei, 1998 J.Neurosci. Q8, 70. Nurrish, Segalat & Kaplan, 1999 Neuron 24, 231. Segalat, Elkes & Kaplan, 1995 Science 267, 1648. We are grateful to Laurent Segalat for
goa-1(
n1134).
snb-1(
md247) was provided by the Caenorhabditis genetics center, which is funded by the NIH National Center for Research Resources.