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.

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.

Metrics

  • 1,810
    views
  • 226
    downloads
  • 14
    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. 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

Share this article

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

Further reading

    1. Neuroscience
    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.

    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.