1. Neuroscience

A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity

  1. TD Barbara Nguyen-Vu  Is a corresponding author
  2. Grace Q Zhao
  3. Subhaneil Lahiri
  4. Rhea R Kimpo
  5. Hanmi Lee
  6. Surya Ganguli
  7. Carla J Shatz
  8. Jennifer L Raymond  Is a corresponding author
  1. Stanford School of Medicine, United States
https://doi.org/10.7554/eLife.20147
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Cite this article
  1. TD Barbara Nguyen-Vu
  2. Grace Q Zhao
  3. Subhaneil Lahiri
  4. Rhea R Kimpo
  5. Hanmi Lee
  6. Surya Ganguli
  7. Carla J Shatz
  8. Jennifer L Raymond
(2017)
A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity
eLife 6:e20147.
https://doi.org/10.7554/eLife.20147
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Abstract

Across many studies, animals with enhanced synaptic plasticity exhibit either enhanced or impaired learning, raising a conceptual puzzle: how enhanced plasticity can yield opposite learning outcomes? Here we show that recent history of experience can determine whether mice with enhanced plasticity exhibit enhanced or impaired learning in response to the same training. Mice with enhanced cerebellar LTD, due to double knockout (DKO) of MHCI H2-Kb/H2-Db (KbDb-/-), exhibited oculomotor learning deficits. However, the same mice exhibited enhanced learning after appropriate pre-training. Theoretical analysis revealed that synapses with history-dependent learning rules could recapitulate the data, and suggested that saturation may be a key factor limiting the ability of enhanced plasticity to enhance learning. Moreover, optogenetic stimulation designed to saturate LTD produced the same impairment in WT as observed in DKO mice. Overall, our results suggest that recent history of activity and the threshold for synaptic plasticity conspire to effect divergent learning outcomes.

Article and author information

Author details

  1. TD Barbara Nguyen-Vu

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    For correspondence
    ngbabs@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4708-1982

  2. Grace Q Zhao

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  3. Subhaneil Lahiri

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2028-6635

  4. Rhea R Kimpo

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  5. Hanmi Lee

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  6. Surya Ganguli

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  7. Carla J Shatz

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    Competing interests
    No competing interests declared.

  8. Jennifer L Raymond

    Department of Neurobiology, Stanford School of Medicine, Stanford, United States
    For correspondence
    jenr@stanford.edu
    Competing interests
    Jennifer L Raymond, Reviewing editor, eLife.

Funding

National Institutes of Health (RO1DC04154,RO1NS072406,R21NS057488,P30DC10363)

  • Jennifer L Raymond

National Science Foundation (Graduate Research Fellowship)

  • TD Barbara Nguyen-Vu

Burroughs Wellcome Fund

  • Surya Ganguli

Genentech Foundation

  • Hanmi Lee

James S. McDonnell Foundation

  • Jennifer L Raymond

National Institutes of Health (F31DC010547)

  • TD Barbara Nguyen-Vu

National Institutes of Health (F32NS058060)

  • Grace Q Zhao

National Institutes of Health (RO1MH07166)

  • Carla J Shatz

National Institutes of Health (NS069375)

  • Jennifer L Raymond

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental procedures were approved by the Administrative Panel on Laboratory Animal Care at Stanford University under animal care and use committee (IACUC) Protocol #9143, titled 'Vestibular and Visual Control of Eye Movements in Mice'.

Copyright

© 2017, Nguyen-Vu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. TD Barbara Nguyen-Vu
  2. Grace Q Zhao
  3. Subhaneil Lahiri
  4. Rhea R Kimpo
  5. Hanmi Lee
  6. Surya Ganguli
  7. Carla J Shatz
  8. Jennifer L Raymond
(2017)
A saturation hypothesis to explain both enhanced and impaired learning with enhanced plasticity
eLife 6:e20147.
https://doi.org/10.7554/eLife.20147

Share this article

https://doi.org/10.7554/eLife.20147

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