Telencephalic outputs from the medial entorhinal cortex are copied directly to the hippocampus

Abstract

Complementary actions of the neocortex and the hippocampus enable encoding and long-term storage of experience dependent memories. Standard models for memory storage assume that sensory signals reach the hippocampus from superficial layers of the entorhinal cortex (EC). Deep layers of the EC on the other hand relay hippocampal outputs to the telencephalic structures including many parts of the neocortex. Here we show that cells in Layer 5a of the medial EC send a copy of their telencephalic outputs back to the CA1 region of the hippocampus. Combining cell-type specific anatomical tracing with high-throughput RNA-sequencing based projection mapping and optogenetics aided circuit mapping, we show that in the mouse brain these projections have a unique topography and target hippocampal pyramidal cells and interneurons. Our results suggest that projections of deep medial EC neurons are anatomically configured to influence the hippocampus and neocortex simultaneously and therefore lead to novel hypotheses on the functional role of the deep EC.

Data availability

On publication data and analysis scripts will be made publicly available via University of Edinburgh's Datashare service (http://datashare.is.ed.ac.uk/). This is an online data repository maintained by the University. MAPseq data will be made available at NLM Sequence Read Archive BioProject.

Article and author information

Author details

  1. Sau Yee Tsoi

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  2. Merve Oncul

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  3. Ella Svahn

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  4. Mark Robertson

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  5. Zuzanna Bogdanowicz

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    No competing interests declared.
  6. Christina McClure

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    Christina McClure, is affiliated with VectorBuilder Inc.. The author has no financial interests to declare..
  7. Gulsen Surmeli

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    gsurmeli@ed.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3227-0641

Funding

Wellcome Trust (211236/Z/18/Z)

  • Gulsen Surmeli

Royal Society (211236/Z/18/Z)

  • Gulsen Surmeli

Biotechnology and Biological Sciences Research Council (BB/M025454/1)

  • Christina McClure

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

Ethics

Animal experimentation: All animal experiments were approved by the University of Edinburgh animal welfarecommittee and were performed under a UK Home Office project license.

Reviewing Editor

  1. Lisa Giocomo, Stanford School of Medicine, United States

Publication history

  1. Preprint posted: March 11, 2021 (view preprint)
  2. Received: August 18, 2021
  3. Accepted: February 4, 2022
  4. Accepted Manuscript published: February 21, 2022 (version 1)
  5. Version of Record published: March 22, 2022 (version 2)

Copyright

© 2022, Tsoi 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. Sau Yee Tsoi
  2. Merve Oncul
  3. Ella Svahn
  4. Mark Robertson
  5. Zuzanna Bogdanowicz
  6. Christina McClure
  7. Gulsen Surmeli
(2022)
Telencephalic outputs from the medial entorhinal cortex are copied directly to the hippocampus
eLife 11:e73162.
https://doi.org/10.7554/eLife.73162
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