Involvement of miR-51 in short-term forgetting via regulating L-AChR in Caenorhabditis elegans

Contrast to the traditional opinion that forgetting is only the opposite of learning and memory, active forgetting explains the intrinsic instability of a labile memory lasting for hours and has the its own signal transduction pathways. However, the detailed mechanisms underlying forgetting are still sparse though the researches available have offered the first insight into the regulation of forgetting. To identify the novel signaling pathway that controlled the process of forgetting, we used the short-term forgetting model of Caenorhabditis elegans and found the involvement of lev-10, a scaffolded transmembrane protein of L-AChR, through screening the candidate genes that potentially functioned in synaptic plasticity. Next, the LEV-9/LEV-10/L-AChR functional complex was confirmed to participate in forgetting occurrence. Furthermore, EGL-9 functioned upstream of LEV-10 and negatively regulated the latter during forgetting. Meanwhile, EGL-9 was also the target of miR-51, and hence mutation of miR-51 similarly affected the function of L-AChR and delayed the short-term forgetting. Our findings in the current study have identified an integrated signaling pathway responsible for the active forgetting, which also provide the new experimental evidences on the cholinergic forgetting signal.