The entorhinal-DG/CA3 pathway in the medial temporal lobe retains visual working memory of a simple surface feature

  1. Weizhen Xie  Is a corresponding author
  2. Marcus Cappiello
  3. Michael A Yassa
  4. Edward Ester
  5. Kareem A Zaghloul
  6. Weiwei Zhang
  1. National Institute of Neurological Disorders and Stroke, United States
  2. University of California, Riverside, United States
  3. University of California, Irvine, United States
  4. University of Nevada Reno, United States
  5. University of California Riverside, United States

Abstract

Classic models consider working memory (WM) and long-term memory as distinct mental faculties that are supported by different neural mechanisms. Yet, there are significant parallels in the computation that both types of memory require. For instance, the representation of precise item-specific memory requires the separation of overlapping neural representations of similar information. This computation has been referred to as pattern separation, which can be mediated by the entorhinal-DG/CA3 pathway of the medial temporal lobe (MTL) in service of long-term episodic memory. However, although recent evidence has suggested that the MTL is involved in WM, the extent to which the entorhinal-DG/CA3 pathway supports precise item-specific WM has remained elusive. Here, we combine an established orientation WM task with high-resolution fMRI to test the hypothesis that the entorhinal-DG/CA3 pathway retains visual WM of a simple surface feature. Participants were retrospectively cued to retain one of the two studied orientation gratings during a brief delay period and then tried to reproduce the cued orientation as precisely as possible. By modeling the delay-period activity to reconstruct the retained WM content, we found that the anterior-lateral entorhinal cortex (aLEC) and the hippocampal DG/CA3 subfield both contain item-specific WM information that is associated with subsequent recall fidelity. Together, these results highlight the contribution of MTL circuitry to item-specific WM representation.

Data availability

Non-identified data (e.g., MTL activities across ROIs and trial-by-trial behavior responses) and custom codes are available via the Open Science Framework repository (https://osf.io/zvdnr/).

Article and author information

Author details

  1. Weizhen Xie

    Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, United States
    For correspondence
    weizhen.xie@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4655-6496
  2. Marcus Cappiello

    Department of Psychology, University of California, Riverside, Riverside, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael A Yassa

    University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8635-1498
  4. Edward Ester

    University of Nevada Reno, Reno, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Kareem A Zaghloul

    Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8575-3578
  6. Weiwei Zhang

    Department of Psychology, University of California Riverside, Riverside, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institute of Mental Health (R01MH117132)

  • Weiwei Zhang

National Institute of Neurological Disorders and Stroke (ZIA-NS003144)

  • Kareem A Zaghloul

National Institute of Neurological Disorders and Stroke (NCFA)

  • Weizhen Xie

National Institute of Neurological Disorders and Stroke (K99NS126492)

  • Weizhen Xie

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

Ethics

Human subjects: Participants provided written informed consent before the study, following the protocol approved by the Internal Review Broad of the University of California, Riverside.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 1,323
    views
  • 240
    downloads
  • 6
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Weizhen Xie
  2. Marcus Cappiello
  3. Michael A Yassa
  4. Edward Ester
  5. Kareem A Zaghloul
  6. Weiwei Zhang
(2023)
The entorhinal-DG/CA3 pathway in the medial temporal lobe retains visual working memory of a simple surface feature
eLife 12:e83365.
https://doi.org/10.7554/eLife.83365

Share this article

https://doi.org/10.7554/eLife.83365

Further reading

    1. Neuroscience
    Jacob A Miller
    Insight

    When navigating environments with changing rules, human brain circuits flexibly adapt how and where we retain information to help us achieve our immediate goals.

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.