RT Journal Article SR Electronic T1 Experience-induced forgetting by WT1 enables learning of sequential tasks JF bioRxiv FD Cold Spring Harbor Laboratory SP 101360 DO 10.1101/101360 A1 Chiara Mariottini A1 Leonardo Munari A1 Ellen Gunzel A1 Joseph M. Seco A1 Nikos Tzavaras A1 Jens Hansen A1 Sarah A. Stern A1 Virginia Gao A1 Georgia E. Hodes A1 Scott J. Russo A1 Vicki Huff A1 Marc Birtwistle A1 Cristina M. Alberini A1 Robert D. Blitzer A1 Ravi Iyengar YR 2017 UL http://biorxiv.org/content/early/2017/03/17/101360.abstract AB Remembering and forgetting are important aspects of normal behavioral adaptation; however, the molecular basis of forgetting has been less studied. Using rat and mouse models we find that WT1, a transcriptional repressor that is activated in the hippocampus by LTP producing stimuli and behavioral memory, enables forgetting. Acute or tonic knockdown of WT1 did not affect short-term memory but enhanced long-term memory and enables a switch from circuit to cellular computation in the hippocampus. A control theory model predicts that WT1 could be a general repressor of memory or a regulator that preserves the ability to remember multiple sequential experiences. Using sequential training for two tasks, mice with non-functional WT1 have better memory for the first task, but show impaired memory for the second task. Taken together, our observations indicate that WT1 mediates an experience-activated forgetting process that preserves the capability of the animal to remember other new experiences.One sentence summary The transcription factor WT1 is a core component of an active forgetting process, and is required for normal behavioral flexibility by allowing LTM for successive experiences.