1. Neuroscience

Theta-phase-specific modulation of dentate gyrus memory neurons

  1. Bahar Rahsepar
  2. Jacob F Norman
  3. Jad Noueihed
  4. Benjamin Lahner
  5. Melanie H Quick
  6. Kevin Ghaemi
  7. Aashna Pandya
  8. Fernando R Fernandez
  9. Steve Ramirez
  10. John A White  Is a corresponding author
  1. Boston University, United States
https://doi.org/10.7554/eLife.82697
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Cite this article
  1. Bahar Rahsepar
  2. Jacob F Norman
  3. Jad Noueihed
  4. Benjamin Lahner
  5. Melanie H Quick
  6. Kevin Ghaemi
  7. Aashna Pandya
  8. Fernando R Fernandez
  9. Steve Ramirez
  10. John A White
(2023)
Theta-phase-specific modulation of dentate gyrus memory neurons
eLife 12:e82697.
https://doi.org/10.7554/eLife.82697
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Abstract

The theta rhythm, a quasi-periodic 4-10 Hz oscillation, is observed during memory processing in the hippocampus, with different phases of theta hypothesized to separate independent streams of information related to the encoding and recall of memories. At the cellular level, the discovery of hippocampal memory cells (engram neurons), as well as the modulation of memory recall through optogenetic activation of these cells, has provided evidence that certain memories are stored, in part, in a sparse ensemble of neurons in the hippocampus. In previous research, however, engram reactivation has been carried out using open loop stimulation at fixed frequencies; the relationship between engram neuron reactivation and ongoing network oscillations has not been taken into consideration. To address this concern, we implemented a closed-loop reactivation of engram neurons that enabled phase-specific stimulation relative to theta oscillations in the local field potential in CA1. Using this real-time approach, we tested the impact of activating dentate gyrus engram neurons during the peak (encoding phase) and trough (recall phase) of theta oscillations. Consistent with previously hypothesized functions of theta oscillations in memory function, we show that stimulating dentate gyrus engram neurons at the trough of theta is more effective in eliciting behavioral recall than either fixed frequency stimulation or stimulation at the peak of theta. Moreover, phase-specific trough stimulation is accompanied by an increase in the coupling between gamma and theta oscillations in CA1 hippocampus. Oure results provide a causal link between phase- specific activation of engram cells and the behavioral expression of memory.

Data availability

Data collected for the purpose of this paper and the custom algorithms that were used in performing the analysis are available at https://dx.doi.org/10.5061/dryad.k0p2ngfc0. The theta-phase detection algorithm is accessible at https://github.com/ndlBU/phase_specific_stim. It can be run using the RTXI platform accessible through http://rtxi.org. Behavioral scoring was done using the ezTrack package available at github.com/DeniseCaiLab/ezTrack.

The following data sets were generated

Article and author information

Author details

  1. Bahar Rahsepar

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Jacob F Norman

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Jad Noueihed

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Benjamin Lahner

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Melanie H Quick

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Kevin Ghaemi

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Aashna Pandya

    Department of Psychological and Brain Sciences, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Fernando R Fernandez

    Department of Biomedical Engineering, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Steve Ramirez

    Department of Psychological and Brain Sciences, Boston University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9966-598X

  10. John A White

    Department of Biomedical Engineering, Boston University, Boston, United States
    For correspondence
    jwhite@bu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1073-2638

Funding

National Institute of Neurological Disorders and Stroke (R01 NS054281)

  • John A White

BU Center for Systems Neuroscience and Neurophotonics Center (Grant)

  • Bahar Rahsepar
  • Jacob F Norman
  • Jad Noueihed
  • Steve Ramirez
  • John A White

National Institute of Biomedical Imaging and Bioengineering (R01 EB016407)

  • John A White

National Institutes of Health (DP5 OD023106-01)

  • Steve Ramirez

National Institutes of Health (Transformative R01)

  • Steve Ramirez

Ludwig Family Foundation (Research Grant)

  • Steve Ramirez

Brain and Behavior Research Foundation (Young Investigator Grant)

  • Steve Ramirez

McKnight Foundation (Memory and Cognitive Disorders Award)

  • Steve Ramirez

Pew Scholars Program in the Biomedical Science (Grant)

  • Steve Ramirez

Air Force Office of Scientific Research (FA9550- 21-1-0310)

  • Steve Ramirez

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (PROTO201800599) of Boston University. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Minnesota (Permit Number: 27-2956). All surgery was performed under sodium pentobarbital anesthesia, and every effort was made to minimize suffering.

Copyright

© 2023, Rahsepar 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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  1. Bahar Rahsepar
  2. Jacob F Norman
  3. Jad Noueihed
  4. Benjamin Lahner
  5. Melanie H Quick
  6. Kevin Ghaemi
  7. Aashna Pandya
  8. Fernando R Fernandez
  9. Steve Ramirez
  10. John A White
(2023)
Theta-phase-specific modulation of dentate gyrus memory neurons
eLife 12:e82697.
https://doi.org/10.7554/eLife.82697

Share this article

https://doi.org/10.7554/eLife.82697

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