Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1

Abstract

Standard models for spatial and episodic memory suggest that the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC) send parallel independent inputs to the hippocampus, each carrying different types of information. Here, we evaluate the possibility that information is integrated between divisions of the entorhinal cortex prior to reaching the hippocampus. We demonstrate that, in mice, fan cells in layer 2 (L2) of LEC that receive neocortical inputs, and that project to the hippocampal dentate gyrus, also send axon collaterals to layer 1 (L1) of the MEC. Activation of inputs from fan cells evokes monosynaptic glutamatergic excitation of stellate and pyramidal cells in L2 of the MEC, typically followed by inhibition that contains fast and slow components mediated by GABAA and GABAB receptors, respectively. Inputs from fan cells also directly activate interneurons in L1 and L2 of MEC, with synaptic connections from L1 interneurons accounting for slow feedforward inhibition of L2 principal cell populations. The relative strength of excitation and inhibition following fan cell activation differs substantially between neurons and is largely independent of anatomical location. Our results demonstrate that the LEC, in addition to directly influencing the hippocampus, can activate or inhibit major hippocampal inputs arising from the MEC. Thus, local circuits in the superficial MEC may combine spatial information with sensory and higher order signals from the LEC, providing a substrate for integration of 'what' and 'where' components of episodic memories.

Data availability

Data is available at: https://datashare.ed.ac.uk/handle/10283/4774Source data and code is available at https://github.com/MattNolanLab/lec_to_mec.

The following data sets were generated
    1. Brianna Vandrey
    (2022) lec_to_mec
    Github, https://github.com/MattNolanLab/lec_to_mec.

Article and author information

Author details

  1. Brianna Vandrey

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Jack Armstrong

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Christina M Brown

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Derek LF Garden

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3336-3791
  5. Matthew F Nolan

    Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom
    For correspondence
    mattnolan@ed.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1062-6501

Funding

Wellcome Trust (200855/Z/16/Z)

  • Matthew F Nolan

Biotechnology and Biological Sciences Research Council (BB/V010107/1)

  • Brianna Vandrey
  • Matthew F Nolan

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

Ethics

Animal experimentation: ll experiments and surgeries were pre-approved by a veterinarian at the Universityof Edinburgh, and conducted under a project licence administered by the UK Home Officeand in accordance with national (Animal [Scientific Procedures] Act, 1986) and international(European Communities Council Directive 2010 (2010/63/EU) legislation governing themaintenance of laboratory animals and their use in scientific research. In reporting results ofanimal research we have aimed to follow the ARRIVE guidelines.

Reviewing Editor

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

Version history

  1. Preprint posted: August 26, 2022 (view preprint)
  2. Received: August 26, 2022
  3. Accepted: December 19, 2022
  4. Accepted Manuscript published: December 23, 2022 (version 1)
  5. Version of Record published: January 6, 2023 (version 2)

Copyright

© 2022, Vandrey 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. Brianna Vandrey
  2. Jack Armstrong
  3. Christina M Brown
  4. Derek LF Garden
  5. Matthew F Nolan
(2022)
Fan cells in lateral entorhinal cortex directly influence medial entorhinal cortex through synaptic connections in layer 1
eLife 11:e83008.
https://doi.org/10.7554/eLife.83008

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https://doi.org/10.7554/eLife.83008

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