MTL neurons phase-lock to human hippocampal theta

  1. Daniel R Schonhaut  Is a corresponding author
  2. Aditya M Rao
  3. Ashwin G Ramayya
  4. Ethan A Solomon
  5. Nora A Herweg
  6. Itzhak Fried
  7. Michael J Kahana  Is a corresponding author
  1. University of Pennsylvania, United States
  2. University of California, Los Angeles, United States

Abstract

Memory formation depends on neural activity across a network of regions, including the hippocampus and broader medial temporal lobe (MTL). Interactions between these regions have been studied indirectly using functional MRI, but the bases for interregional communication at a cellular level remain poorly understood. Here we evaluate the hypothesis that oscillatory currents in the hippocampus synchronize the firing of neurons both within and outside the hippocampus. We recorded extracellular spikes from 1,854 single- and multi-units simultaneously with hippocampal local field potentials (LFPs) in 28 neurosurgical patients who completed virtual navigation experiments. A majority of hippocampal neurons phase-locked to oscillations in the slow (2-4Hz) or fast (6-10Hz) theta bands, with a significant subset exhibiting nested slow theta x beta frequency (13-20Hz) phase-locking. Outside of the hippocampus, phase-locking to hippocampal oscillations occurred only at theta frequencies and primarily among neurons in the entorhinal cortex and amygdala. Moreover, extrahippocampal neurons phase-locked to hippocampal theta even when theta did not appear locally. These results indicate that spike-time synchronization with hippocampal theta is a defining feature of neuronal activity in the hippocampus and structurally connected MTL regions. Theta phase-locking could mediate flexible communication with the hippocampus to influence the content and quality of memories.

Data availability

The data used in this study is publicly available for download from the Cognitive Electrophysiology Data Portal: http://memory.psych.upenn.edu/Electrophysiological_Data. This dataset includes de-identified, raw EEG data, spike-sorted unit data, and preprocessed phase-locking data. All data analysis code and JupyterLab notebooks can be freely downloaded at the public GitHub repositories: https://github.com/pennmem/SchoEtal24_eLife.

Article and author information

Author details

  1. Daniel R Schonhaut

    Department of Neuroscience, University of Pennsylvania, Philadelphia, United States
    For correspondence
    daniel.schonhaut@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8667-031X
  2. Aditya M Rao

    Department of Psychology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ashwin G Ramayya

    Department of Neurosurgery, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4444-0433
  4. Ethan A Solomon

    Department of Bioengineering, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Nora A Herweg

    Department of Psychology, University of Pennsylvania, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4647-7408
  6. Itzhak Fried

    Department of Neurosurgery, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5962-2678
  7. Michael J Kahana

    Department of Psychology, University of Pennsylvania, Philadelphia, United States
    For correspondence
    kahana@psych.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8122-9525

Funding

National Science Foundation Graduate Research Fellowship Program

  • Daniel R Schonhaut

National Institutes of Health (1U01NS113198-01)

  • Michael J Kahana

National Institute of Neurological Disorders and Stroke (R01-NS033221)

  • Itzhak Fried

National Institute of Neurological Disorders and Stroke (R01-NS084017)

  • Itzhak Fried

Deutsche Forschungsgemeinschaft (HE 8302/1-1)

  • Nora A Herweg

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

Reviewing Editor

  1. Caleb Kemere, Rice University, United States

Ethics

Human subjects: All testing was completed under informed consent. Institutional review boards at the University of California, Los Angeles and the University of Pennsylvania approved all experiments. The number of the UCLA IRB protocol on which the Goldmine experiment was conducted is #10-000973.

Version history

  1. Preprint posted: December 20, 2022 (view preprint)
  2. Received: December 22, 2022
  3. Accepted: January 8, 2024
  4. Accepted Manuscript published: January 9, 2024 (version 1)
  5. Version of Record published: March 18, 2024 (version 2)

Copyright

© 2024, Schonhaut 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. Daniel R Schonhaut
  2. Aditya M Rao
  3. Ashwin G Ramayya
  4. Ethan A Solomon
  5. Nora A Herweg
  6. Itzhak Fried
  7. Michael J Kahana
(2024)
MTL neurons phase-lock to human hippocampal theta
eLife 13:e85753.
https://doi.org/10.7554/eLife.85753

Share this article

https://doi.org/10.7554/eLife.85753

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