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