[Toward understanding the molecular mechanism of brain function by molecular and neural circuit elucidation of the C....

Recent studies have provided extensive molecular insights into neuronal polarity establishment in vitro. However, it is still poorly understood how the corresponding phenomenon occurs and leads to correct localization of synaptic components in vivo. RIA interneurons in the nematode C. elegans have a neurite clearly divided into pre- and post-synaptic regions and act as a pivotal component of the neural circuit for thermotaxis behavior, thereby providing a suitable model to elucidate these issues. We found that loss of Inositol Monophosphatase (IMPase) encoded by the ttx-7 gene, an Inositol-producing enzyme regarded as a bipolar disorder-relevant molecule for its Lithium sensitivity, causes defects in thermotaxis behavior and localization of synaptic proteins in RIA neurons in vivo. Both behavioral and localization defects in ttx-7 mutants were rescued by expression of IMPase at the adult stage and Inositol application, and were mimicked by Lithium application in wild type animals. These results suggest that IMPase is required in the mature nervous system for regulating correct localization of synaptic components in the central interneurons in order for animals to behave properly.