Serotonin (5-HT) plays a vital role in a variety of biological functions in C. elegans including egg laying, sensory transduction, dauer formation and male mating behaviour. An essential part of comprehending 5-HT signalling is understanding how it interacts with other neurotransmitters. There is evidence suggesting that 5-HT plays a key role in neuromodulation in C. elegans. Synaptic inhibition of acetylcholine (ACh) release by 5-HT has been demonstrated in the ventral nerve cord [1]. Conversely cholinergic control over 5-HT release is evident in the egg laying circuitry [2]. An antagonistic relationship has been described between 5-HT and dopamine during egg-laying behaviour [3]. Although no specific relationship has been demonstrated between 5-HT and GABA in C. elegans, there is evidence suggesting that both transmitters use similar ion channels [4]. In addition, larvae of the rhabditid nematode Nippostrongylus brasiliensis showed significantly higher levels of 5-HT and dopamine when GABA was not detected [5]. We are undertaking a comprehensive investigation in C. elegans into the relationship between 5-HT and other neurotransmitters both pre- and post-synaptically. Previous work has identified a tryptophan hydroxylase gene (
tph-1) responsible in the production of 5-HT. Using GFP expression and immunoreactivity we are identifying how
tph-1 dysfunction affects genes involved in GABA, Dopamine and ACh signalling and production. Initially, how
tph-1 affects the expression pattern of
unc-47::gfp (VGAT),
unc-49::gfp (GABA receptor),
unc-13::gfp (DAG binding protein) and
unc-17 (VAChT) immunoreactivity. In addition we are looking at how
tph-1::gfp expression is influenced in
cha-1 (ChAT deficient) mutants and serotonergic immunoreactivity in
unc-25 (GAD deficient),
unc-17,
cha-1,
cat-2 (tyrosine hydroxylase deficient) mutants. Finally, we are examining the relationship between 5-HT and the neurotransmitters; Dopamine, ACh and GABA in the dauer formation pathway. 1. Nurrish, S., L. Segalat, and J.M. Kaplan, Neuron, 1999. 24(1): p. 231-242; 2. Schafer, W.R., B.M. Sanchez, and C.J. Kenyon, Genetics, 1996. 143: p. 1219-1230; 3. Weinshenker, D., G. Garriga, and J.H. Thomas, J of Neurosci., 1995. 15: p. 6975-6985; 4. Ranganathan, R., S.C. Cannon, and H.R. Horvitz, Nature, 2000. 408: p. 470-475; 5. Barreteau, H., et al., Comp. Biochem & Physiol. C: 1991. 100: p. 445-449; 6. Sze, J.Y., et al., Nature, 2000. 403: p. 560-564.