Molecular mechanisms of forgetting in caenorhabditis elegans

A plastic nervous system requires not only the ability to acquire and store but also to forget. Here we report that musashi (msi-1) is necessary for time-dependent memory loss in C. elegans. Tissue specific rescue demonstrates that MSI-1 function is necessary in the AVA interneuron. Using RNA-IP, we found that MSI-1 binds to mRNAs of three subunits of the Arp2/3 actin branching regulator complex in vivo and downregulates ARX-1, ARX-2 and ARX-3 translation upon associative learning. The role of msi-1 in forgetting is also reflected by the persistence of learning induced GLR-1 synaptic size increase in msi-1 mutants. We demonstrate that memory length is regulated cooperatively through the activation of adducin (add-1) and by the inhibitory effect of msi-1. Thus, a GLR-1/MSI-1/Arp2/3 pathway induces forgetting and represents a novel mechanism of memory decay by linking translational control to the structure of the actin cytoskeleton in neurons.