A mobile circular DNA element drives memory-related processes in mice

Haobin Ren; Hao Gong; Wei-Siang Liau; Qiongyi Zhao; Alexander P. Walsh; Mason R.B. Musgrove; Joshua W.A. Davies; Esmi L. Zajackowski; Sachithrani U. Madugalle; Paul R. Marshall; Tian Lan; Jichun Shi; Jiazhi Jiang; Wei Wei; Xiang Li; Timothy W. Bredy

doi:10.1101/2025.09.17.676936

NeurosciencebioRxivSep 17, 2025

Preprint

A mobile circular DNA element drives memory-related processes in mice

Haobin Ren iD, Hao Gong iD, Wei-Siang Liau iD, Qiongyi Zhao iD, Alexander P. Walsh iD, Mason R.B. Musgrove iD, Joshua W.A. Davies iD, Esmi L. Zajackowski iD, Sachithrani U. Madugalle iD, Paul R. Marshall iD, Tian Lan, Jichun Shi iD, Jiazhi Jiang iD, Wei Wei iD, Xiang Li iD, Timothy W. Bredy iD

Abstract

Extrachromosomal circular DNAs (ecDNAs) are double stranded, closed loop DNA molecules that act independently of the genome. Here we report the discovery of a brain-enriched ecDNA, ecCldn34d, that regulates the transcriptional state of plasticity-related genes and is temporally associated with the stability of fear memories. ecDNA therefore represents a novel class of mobile DNA elements that are involved in experience-dependent neuroadaptation.

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