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  • Perspective
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Assessments of dentate gyrus function: discoveries and debates

Nature Reviews Neuroscience volume 24, pages 502–517 (2023)Cite this article

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Abstract

There has been considerable speculation regarding the function of the dentate gyrus (DG) — a subregion of the mammalian hippocampus — in learning and memory. In this Perspective article, we compare leading theories of DG function. We note that these theories all critically rely on the generation of distinct patterns of activity in the region to signal differences between experiences and to reduce interference between memories. However, these theories are divided by the roles they attribute to the DG during learning and recall and by the contributions they ascribe to specific inputs or cell types within the DG. These differences influence the information that the DG is thought to impart to downstream structures. We work towards a holistic view of the role of DG in learning and memory by first developing three critical questions to foster a dialogue between the leading theories. We then evaluate the extent to which previous studies address our questions, highlight remaining areas of conflict, and suggest future experiments to bridge these theories.

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Fig. 1: Schematic of mechanisms driving each proposed theory of dentate gyrus function.
Fig. 2: Leading theory compatibility.

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Acknowledgements

This work was partially supported by the NSF DMS-1042134, NIH R03MH120406, NIH R01 NS039456, NRF 2021R1A4A2001803, NRF 2019R1A2C2088799, NRF 2022M3E5E8017723, the NIH Institute of Neural Computation/Biology T32 MH020002 and the Kavli Institute for Brain and Mind. The authors gratefully thank D. Nitz, L.K. Quinn, J.W. Rueckemann, T. Johnson, P. Riviere and C. Heyman for insightful discussions and editorial assistance.

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Authors and Affiliations

  1. Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA

    Mia Borzello & Lara M. Rangel

  2. Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA

    Steve Ramirez

  3. Cognitive Neuroscience, SISSA, Trieste, Italy

    Alessandro Treves

  4. Department of Brain and Cognitive Sciences, Seoul National University, Seoul, South Korea

    Inah Lee

  5. Departments of Child and Adolescent Psychiatry, Neuroscience and Physiology and Psychiatry and the Neuroscience Institute, New York University Langone Health, New York, NY, USA

    Helen Scharfman

  6. The Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA

    Helen Scharfman

  7. Department of Neurobiology and Behaviour, University of California, Irvine, Irvine, CA, USA

    Craig Stark

  8. Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA

    James J. Knierim

  9. Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, USA

    James J. Knierim

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Borzello, M., Ramirez, S., Treves, A. et al. Assessments of dentate gyrus function: discoveries and debates. Nat. Rev. Neurosci. 24, 502–517 (2023). https://doi.org/10.1038/s41583-023-00710-z

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