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Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body

Nature Neuroscience volume 10, pages 1578–1586 (2007)Cite this article

Abstract

In humans and many other animals, memory consolidation occurs through multiple temporal phases and usually involves more than one neuroanatomical brain system. Genetic dissection of Pavlovian olfactory learning in Drosophila melanogaster has revealed multiple memory phases, but the predominant view holds that all memory phases occur in mushroom body neurons. Here, we demonstrate an acute requirement for NMDA receptors (NMDARs) outside of the mushroom body during long-term memory (LTM) consolidation. Targeted dsRNA-mediated silencing of Nmdar1 and Nmdar2 (also known as dNR1 or dNR2, respectively) in cholinergic R4m-subtype large-field neurons of the ellipsoid body specifically disrupted LTM consolidation, but not retrieval. Similar silencing of functional NMDARs in the mushroom body disrupted an earlier memory phase, leaving LTM intact. Our results clearly establish an anatomical site outside of the mushroom body involved with LTM consolidation, thus revealing both a distributed brain system subserving olfactory memory formation and the existence of a system-level memory consolidation in Drosophila.

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Figure 1: dsRNA-mediated knockdown of dNR2 in adult brain.
Figure 2: Functional NMDARs in the ellipsoid body are required for LTM.
Figure 3: Inducible knockdown of dNR2 specifically blocks consolidation and storage, but not retrieval, of protein synthesis–dependent LTM.
Figure 4: Overexpression of dNR2 in the ellipsoid body enhances 1-d memory.
Figure 5: Transference of memory from the mushroom body to the ellipsoid body during LTM consolidation.
Figure 6: NMDAR function in the mushroom body is required for MTM but not for LTM.

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Acknowledgements

We thank G. Korge, Y. Zhong, L. Luo and Bloomington Fly Center for fly stocks. We also thank M. Heisenberg, H. Cline and J. Dubnau for comments and discussion. This work was supported by grants to T.T. from the US National Institutes of Health and Dart Neurosciences, LLC, and to A.-S.C. from the National Science Council, the Brain Research Center of the University System of Taiwan and the Technology Development Program of Ministry of Economy.

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Author notes

  1. Daniel Leong

    Present address: Present address: Department of Biomedical Engineering, City College of New York, 138th Street and Convent Avenue, New York, New York 10031, USA.,

  2. Chia-Lin Wu and Shouzhen Xia: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Biotechnology and Department of Life Science, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan

    Chia-Lin Wu, Tsai-Feng Fu, Ying-Hsiu Chen & Ann-Shyn Chiang

  2. Brain Research Center, National Tsing Hua University, University System of Taiwan, 101, Section 2, Kuang-Fu Road, Hsinchu, 30013, Taiwan

    Chia-Lin Wu, Tsai-Feng Fu, Ying-Hsiu Chen & Ann-Shyn Chiang

  3. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, 11724, New York, USA

    Shouzhen Xia, Huaien Wang, Daniel Leong & Tim Tully

  4. Department of Applied Chemistry, National Chi Nan University, University Road, Puli, 545, Nantou, Taiwan

    Tsai-Feng Fu

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Contributions

C.-L.W. and S.X. conceived and designed the experiments. C.-L.W., S.X. and T.-F.F. carried out the experiments with technique support from H.W., D.L. and Y.-H.C. C.-L.W., S.X. and A.-S.C. analyzed the data. C.-L.W. and S.X. graphed the data. S.X. and T.T. wrote the paper.

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Correspondence to Ann-Shyn Chiang or Tim Tully.

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Wu, CL., Xia, S., Fu, TF. et al. Specific requirement of NMDA receptors for long-term memory consolidation in Drosophila ellipsoid body. Nat Neurosci 10, 1578–1586 (2007). https://doi.org/10.1038/nn2005

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