Neuronally produced betaine acts via a ligand-gated ion channel to control behavioral states

Trimethylglycine, or betaine, is an amino acid derivative found in diverse organisms, from bacteria to plants and animals, with well-established functions as a methyl donor and osmolyte in all cells. In addition, betaine is found in the nervous system, though its function there is not well understood. Here, we show that betaine is synthesized in the nervous system of the nematode worm, Caenorhabditis elegans, where it functions in the control of different behavioral states. Specifically, we find that betaine can be produced in a pair of interneurons, the RIMs, and packed into synaptic vesicles by the vesicular monoamine transporter, CAT-1, expressed in these cells. Mutant animals defective in betaine synthesis are unable to control the switch from local to global foraging, a phenotype that can be rescued by restoring betaine specifically to the RIM neurons. These effects on behavior are mediated by a newly identified betaine-gated chloride channel, LGC-41, which is expressed broadly in the navigation circuit. These results implicate neuronally produced betaine as a neuromodulator in vivo and suggest a potentially similar role for betaine in nervous systems of other animals.