Zhang, Yun, Liu, He, Canales, Xicotencatl Gracida, Wu, Min, Choi, Myung-gyu, Calarco, John A., Duan, Fengyun, Wu, Taihong
[
International Worm Meeting,
2021]
Animals generate adaptive behaviors to the changing environment. For example, when some cues are associated with dangers, animals form an aversive memory of the cues. If the association is not consolidated or further strengthened, the memory dissipates over time and animals forget. However, it is not understood whether the forgetting process is the reverse of the learning process and whether the brain state returns to the naive state after forgetting. Here, we address these questions by analyzing the forgetting of pathogenic bacteria-induced aversive memory in adult C. elegans. We find that forgetting forms a novel brain state that is different from the naive and the learned states at the levels of behavior, neuronal circuity and gene expression. Interestingly, although worms after forgetting respond to the pathogenic bacteria similarly to naive worms, the aversive memory can be acutely reactivated. To understand the circuity and molecular mechanisms of forgetting, we performed behavioral assay and in vivo calcium imaging in combination with genetic perturbations. We find that the interneuron RIA, which is important for the learning of pathogenic bacteria, also plays a key role in forgetting. Two receptors, which are enriched in the pre- and post-synaptic regions of RIA respectively, antagonistically regulate the speed of forgetting. Thus, our study for the first time systematically shows that forgetting produces a novel state that can be rapidly induced to generate the learned behavior. Our findings on the neuronal mechanisms of forgetting not only better our understanding of the cognitive function of the brain, but also shed light on potential defects associated with forgetting-related mental disorders.