Genetic dissection of mutual interference between two consecutive learning tasks in Drosophila

Animals can continuously learn different tasks to adapt to changing environments and, therefore, have strategies to effectively cope with inter-task interference, including both proactive interference (Pro-I) and retroactive interference (Retro-I). Many biological mechanisms are known to contribute to learning, memory, and forgetting for a single task, however, mechanisms involved only when learning sequential different tasks are relatively poorly understood. Here, we dissect the respective molecular mechanisms of Pro-I and Retro-I between two consecutive associative learning tasks in Drosophila. Pro-I is more sensitive to an inter-task interval (ITI) than Retro-I. They occur together at short ITI (<20 min), while only Retro-I remains significant at ITI beyond 20 min. Acutely overexpressing Corkscrew (CSW), an evolutionarily conserved protein tyrosine phosphatase SHP2, in mushroom body (MB) neurons reduces Pro-I, whereas acute knockdown of CSW exacerbates Pro-I. Such function of CSW is further found to rely on the ? subset of MB neurons and the downstream Raf/MAPK pathway. In contrast, manipulating CSW does not affect Retro-I as well as a single learning task. Interestingly, manipulation of Rac1, a molecule that regulates Retro-I, does not affect Pro-I. Thus, our findings suggest that learning different tasks consecutively triggers distinct molecular mechanisms to tune proactive and retroactive interference.

Automated summary

Animals have strategies to cope with proactive and retroactive interference when learning different tasks consecutively. In this study, researchers investigated the molecular mechanisms of proactive and retroactive interference in Drosophila. They found that proactive interference is more sensitive to the inter-task interval (ITI) and that manipulating the protein tyrosine phosphatase SHP2 affects proactive interference but not retroactive interference or single learning tasks. These findings suggest that sequential learning of different tasks triggers distinct molecular mechanisms to tune proactive and retroactive interference.