Disrupting the hippocampal Piwi pathway enhances contextual fear memory in mice

Laura J. Leighton, Wei Wei, Paul R. Marshall, Vikram Singh Ratnu, Xiang Li, Esmi L. Zajaczkowski, Paola A. Spadaro, Nitin Khandelwal, Arvind Kumar, Timothy W. Bredy

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The Piwi pathway is a conserved gene regulatory mechanism comprised of Piwi-like proteins and Piwi-interacting RNAs, which modulates gene expression via RNA interference and through interaction with epigenetic mechanisms. The mammalian Piwi pathway has been defined by its role in transposon control during spermatogenesis; however, despite an increasing number of studies demonstrating its expression in the nervous system, relatively little is known about its function in neurons or potential contribution to behavioural regulation. We have discovered that all three Piwi-like genes are expressed in the adult mouse brain, and that viral-mediated knockdown of the Piwi-like genes Piwil1 and Piwil2 in the dorsal hippocampus leads to enhanced contextual fear memory without affecting generalised anxiety. These results implicate the Piwi pathway in behavioural regulation in the adult mammalian brain, likely through modulation of plasticity-related gene expression.

Original languageEnglish (US)
Pages (from-to)202-209
Number of pages8
JournalNeurobiology of Learning and Memory
StatePublished - May 2019
Externally publishedYes


  • Epigenetics
  • Learning
  • Memory
  • Molecular biology
  • Noncoding RNA
  • Plasticity

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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