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Metaplasticity contributes to memory formation in the hippocampus

Neuropsychopharmacologyvolume 44pages408414 (2019) | Download Citation


Prior learning can modify the plasticity mechanisms that are used to encode new information. For example, NMDA receptor (NMDAR) activation is typically required for new spatial and contextual learning in the hippocampus. However, once animals have acquired this information, they can learn new tasks even if NMDARs are blocked. This finding suggests that behavioral training alters cellular plasticity mechanisms such that NMDARs are not required for subsequent learning. The mechanisms that mediate this change are currently unknown. To address this issue, we tested the idea that changes in intrinsic excitability (induced by learning) facilitate the encoding of new memories via metabotropic glutamate receptor (mGluR) activation. Consistent with this hypothesis, hippocampal neurons exhibited increases in intrinsic excitability after learning that lasted for several days. This increase was selective and only observed in neurons that were activated by the learning event. When animals were trained on a new task during this period, excitable neurons were reactivated and memory formation required the activation of mGluRs instead of NMDARs. These data suggest that increases in intrinsic excitability may serve as a metaplastic mechanism for memory formation.

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These experiments were supported by a Whitehall Foundation Research Grant to B.J.W. and a CNPq/Brazil graduate fellowship to A.P.C. “SWE Process: 202250/2015-6”.

Author information

Author notes

  1. These authors contributed equally: Ana P. Crestani, Jamie N. Krueger


  1. Neuroscience Graduate Program, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    • Ana P. Crestani
  2. Neuroscience Graduate Program, University of California, Davis, Davis, CA, USA

    • Jamie N. Krueger
    •  & Eden V. Barragan
  3. Center for Neuroscience, University of California, Davis, Davis, CA, USA

    • Yuki Nakazawa
    • , John A. Gray
    •  & Brian J. Wiltgen
  4. Department of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, CA, USA

    • Sonya E. Nemes
  5. Department of Biophysics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    • Jorge A. Quillfeldt
  6. Department of Neurology, University of California, Davis, Davis, CA, USA

    • John A. Gray
  7. Department of Psychology, University of California, Davis, Davis, CA, USA

    • Brian J. Wiltgen


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The authors declare no competing interests.

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Correspondence to Brian J. Wiltgen.

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