Hippocampal metaplasticity is required for the formation of temporal associative memories

Jian Xu, Marcia D. Antion, Toshihiro Nomura, Stephen Kraniotis, Yongling Zhu, Anis Contractor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories.

Original languageEnglish (US)
Pages (from-to)16762-16773
Number of pages12
JournalJournal of Neuroscience
Issue number50
StatePublished - Dec 10 2014


  • Endocannabinoid
  • Memory
  • Metaplasticity
  • mGluR5

ASJC Scopus subject areas

  • General Neuroscience


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