Letter | Published:

Engineering a memory with LTD and LTP

Nature volume 511, pages 348352 (17 July 2014) | Download Citation

Abstract

It has been proposed that memories are encoded by modification of synaptic strengths through cellular mechanisms such as long-term potentiation (LTP) and long-term depression (LTD)1. However, the causal link between these synaptic processes and memory has been difficult to demonstrate2. Here we show that fear conditioning3,4,5,6,7,8, a type of associative memory, can be inactivated and reactivated by LTD and LTP, respectively. We began by conditioning an animal to associate a foot shock with optogenetic stimulation of auditory inputs targeting the amygdala, a brain region known to be essential for fear conditioning3,4,5,6,7,8. Subsequent optogenetic delivery of LTD conditioning to the auditory input inactivates memory of the shock. Then subsequent optogenetic delivery of LTP conditioning to the auditory input reactivates memory of the shock. Thus, we have engineered inactivation and reactivation of a memory using LTD and LTP, supporting a causal link between these synaptic processes and memory.

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Acknowledgements

We thank J. Isaacson, L. Squire and members of the Malinow laboratory for suggestions. This study was supported by NIH MH049159 and Cure Alzheimer’s Foundation grants to R.M. and NIH grant NS27177 to R.T.; R.T. is an Investigator of the HHMI.

Author information

Author notes

    • Sadegh Nabavi
    •  & Rocky Fox

    These authors contributed equally to this work.

Affiliations

  1. Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, University of California at San Diego, California 92093, USA

    • Sadegh Nabavi
    • , Rocky Fox
    • , Christophe D. Proulx
    •  & Roberto Malinow
  2. Department of Pharmacology, University of California at San Diego, California 92093, USA

    • John Y. Lin
    •  & Roger Y. Tsien
  3. Howard Hughes Medical Institute, University of California at San Diego, California 92093, USA

    • Roger Y. Tsien

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Contributions

S.N. and R.M. designed the experiments and wrote the manuscript. S.N., R.F. and R.M. analysed the data. S.N., R.F. and C.D.P. performed the experiments. J.Y.L. and R.Y.T. provided the oChIEF-tdTomato construct.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Roberto Malinow.

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DOI

https://doi.org/10.1038/nature13294

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