The immediate early gene Arc is not required for hippocampal long-term potentiation

Madeleine Kyrke-Smith, Lenora J. Volk, Samuel F. Cooke, Mark F. Bear, Richard L. Huganir, Jason D. Shepherd

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Memory consolidation is thought to occur through protein synthesis-dependent synaptic plasticity mechanisms such as longterm potentiation (LTP). Dynamic changes in gene expression and epigenetic modifications underlie the maintenance of LTP. Similar mechanisms may mediate the storage of memory. Key plasticity genes, such as the immediate early gene Arc, are induced by learning and by LTP induction. Mice that lack Arc have severe deficits in memory consolidation, and Arc has been implicated in numerous other forms of synaptic plasticity, including long-term depression and cell-to-cell signaling. Here, we take a comprehensive approach to determine if Arc is necessary for hippocampal LTP in male and female mice. Using a variety of Arc knock-out (KO) lines, we found that germline Arc KO mice show no deficits in CA1 LTP induced by high-frequency stimulation and enhanced LTP induced by theta-burst stimulation. Temporally restricting the removal of Arc to adult animals and spatially restricting it to the CA1 using Arc conditional KO mice did not have an effect on any form of LTP. Similarly, acute application of Arc antisense oligodeoxynucleotides had no effect on hippocampal CA1 LTP. Finally, the maintenance of in vivo LTP in the dentate gyrus of Arc KO mice was normal. We conclude that Arc is not necessary for hippocampal LTP and may mediate memory consolidation through alternative mechanisms.

Original languageEnglish (US)
Pages (from-to)4202-4211
Number of pages10
JournalJournal of Neuroscience
Issue number19
StatePublished - May 12 2021


  • Arc
  • Hippocampus
  • LTP
  • Memory
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)


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