Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons

  • Nature Neurosciencevolume 21pages258269 (2018)
  • doi:10.1038/s41593-017-0061-5
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Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory.

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We thank M. Wong, B.L. Boublil, N. Beer and A.-L. Schlenner for technical assistance; and we thank K.B. Fischer and L.A. Ewell for SWR detection analysis code. We also thank the following UCSD students for help with behavioral testing and microscopy: R. Brar, M. Josic, A. Kappe, S. Lum, C. Miller, D. Moller and L. Piper. This research was supported by NIH grant MH102841 to J.E.L. and J.L.; NIH grant MH100349 and a Walter F. Heiligenberg Professorship to J.L.; NIH grants MH100354, NS084324, NS086947, NS097772 and NS102915 to S.L.; a JSPS Postdoctoral Fellowship for Research Abroad, Precursory Research for Embryonic Science and Technology (PRESTO) from Japan Science and Technology Agency (JST) and Kaken-hi grants 17H05939, and 17H05551 to T.S.; and a PEW Postdoctoral Fellowship to V.P.

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Author notes

  1. Takyua Sasaki and Verónica C. Piatti contributed equally to this work.

  2. Deceased: John E. Lisman.


  1. Neurobiology Section and Center for Neural Circuits and Behavior, Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA

    • Takuya Sasaki
    • , Verónica C. Piatti
    • , Ernie Hwaun
    • , Siavash Ahmadi
    • , Stefan Leutgeb
    •  & Jill K. Leutgeb
  2. Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan

    • Takuya Sasaki
  3. Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Kawaguchi, Japan

    • Takuya Sasaki
  4. Department of Biology, Brandeis University, Waltham, MA, USA

    • John E. Lisman
  5. Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, CA, USA

    • Stefan Leutgeb


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T.S., V.C.P., S.L. and J.K.L. designed experiments. V.C.P. developed the lesion and performed the behavioral testing and dentate electrophysiological recording experiments. S.A. performed preliminary analyses of dentate recordings. T.S. performed CA3 electrophysiological recordings and behavior in DG-lesioned animals, with assistance from E.H. with behavior, histology and microscopy. T.S. performed all reported analyses. J.E.L. provided conceptual discussions. T.S., S.L. and J.K.L. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jill K. Leutgeb.

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