PHARMACOLOGICAL CHARACTERISATION OF NOVEL DOPAMINERGIC LIGAND-GATED ION CHANNELS IN <EM>C. ELEGANS</EM>

Despite a comparatively small nervous system consisting of only 302 neurons, the nematode C. elegans exhibits a diverse behavioural repertoire, and has demonstrated its capability to perform complex tasks like maze navigation. This raises the question as to how small-scale networks can support such functionality.
The C. elegans genome encodes over one hundred genes for pentameric ligand-gated ion channels (pLGICs); more than double of that in humans. Classical mammalian pLGICs including nAChRs and GABA_ARs are well characterised. As well as classical pLGICs, atypical receptors including excitatory and inhibitory receptors for monoamines, are also expressed in C. elegans. Many putative pLGICs genes remain uncharacterised.
To identify ligands for these orphan receptors we have systematically screened pLGICs using Two Electrode Voltage Clamp (TEVC) in Xenopus oocytes. This has revealed a new family of excitatory pLGICs that are gated by dopamine. Further pharmacological characterisation is currently underway to confirm that dopamine is indeed the primary endogenous ligand for these receptors.
Dopaminergic signalling in C. elegans plays a crucial role in the modulation of locomotion and learning related behaviours, governed in particular by eight mechanosensory dopaminergic neurons. Delineating the function of the dopaminergic system is of particular interest, and this work contributes understanding towards how anatomically small nervous systems can support diverse behaviours and reveals complexity in superficially simplistic networks.