Local projections of layer Vb-to-Va are more prominent in lateral than in medial entorhinal cortex

  1. Shinya Ohara  Is a corresponding author
  2. Stefan Blankvoort
  3. Rajeevkumar Raveendran Nair
  4. Maximiliano J Nigro
  5. Eirik S Nilssen
  6. Cliff Kentros
  7. Menno P Witter  Is a corresponding author
  1. Tohoku University Graduate School of Life Sciences, Japan
  2. Norwegian University of Science and Technology, Norway

Abstract

The entorhinal cortex, in particular neurons in layer V, allegedly mediate transfer of information from the hippocampus to the neocortex, underlying long-term memory. Recently, this circuit has been shown to comprise a hippocampal output recipient layer Vb and a cortical projecting layer Va. With the use of in vitro electrophysiology in transgenic mice specific for layer Vb, we assessed the presence of the thus necessary connection from layer Vb-to-Va in the functionally distinct medial (MEC) and lateral (LEC) subdivisions; MEC, particularly its dorsal part, processes allocentric spatial information, whereas the corresponding part of LEC processes information representing elements of episodes. Using identical experimental approaches, we show that connections from layer Vb-to-Va neurons are stronger in dorsal LEC compared with dorsal MEC, suggesting different operating principles in these two regions. Although further in vivo experiments are needed, our findings imply a potential difference in how LEC and MEC mediate episodic systems-consolidation.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. We provide source data for Figure 1, 2, 3, 4, 5, Figure1-figure supplement 2, and Figure4-figure supplement 2.

Article and author information

Author details

  1. Shinya Ohara

    Laboratory of Systems Neuroscience, Tohoku University Graduate School of Life Sciences, Sendai, Japan
    For correspondence
    shinyaohara@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0681-5086
  2. Stefan Blankvoort

    Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3850-3829
  3. Rajeevkumar Raveendran Nair

    Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  4. Maximiliano J Nigro

    Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  5. Eirik S Nilssen

    Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6997-3343
  6. Cliff Kentros

    Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  7. Menno P Witter

    Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
    For correspondence
    menno.witter@ntnu.no
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0285-1637

Funding

Kavli Foundation (endowment)

  • Menno P Witter

Norwegian Research Council (infrastructure grant NORBRAIN,#197467)

  • Menno P Witter

Norwegian Research Council (the Centre of Excellence scheme - Centre for Neural Computation,#223262)

  • Menno P Witter

Norwegian Research Council (research grant,# 227769)

  • Menno P Witter

Ministry of Education, Culture, Sports, Science and Technology (KAKENHI,#19K06917)

  • Shinya Ohara

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 experiments were approved by the local ethics committee and were in accordance with the European Communities Council Directive and the Norwegian Experiments on Animals Act (#17898, #22312).

Reviewing Editor

  1. Katalin Toth, University of Ottawa, Canada

Publication history

  1. Received: February 5, 2021
  2. Accepted: March 25, 2021
  3. Accepted Manuscript published: March 26, 2021 (version 1)
  4. Version of Record published: April 16, 2021 (version 2)

Copyright

© 2021, Ohara 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

  • 1,516
    Page views
  • 212
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Shinya Ohara
  2. Stefan Blankvoort
  3. Rajeevkumar Raveendran Nair
  4. Maximiliano J Nigro
  5. Eirik S Nilssen
  6. Cliff Kentros
  7. Menno P Witter
(2021)
Local projections of layer Vb-to-Va are more prominent in lateral than in medial entorhinal cortex
eLife 10:e67262.
https://doi.org/10.7554/eLife.67262

Further reading

    1. Neuroscience
    Orie T Shafer et al.
    Research Article

    The circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order and optimal timing across the day. In animals, a central brain clock coordinates circadian rhythms throughout the body and is characterized by a remarkable robustness that depends on synaptic connections between constituent neurons. The clock neuron network of Drosophila, which shares network motifs with clock networks in the mammalian brain yet is built of many fewer neurons, offers a powerful model for understanding the network properties of circadian timekeeping. Here we report an assessment of synaptic connectivity within a clock network, focusing on the critical lateral neuron (LN) clock neuron classes within the Janelia hemibrain dataset. Our results reveal that previously identified anatomical and functional subclasses of LNs represent distinct connectomic types. Moreover, we identify a small number of non-clock cell subtypes representing highly synaptically coupled nodes within the clock neuron network. This suggests that neurons lacking molecular timekeeping likely play integral roles within the circadian timekeeping network. To our knowledge, this represents the first comprehensive connectomic analysis of a circadian neuronal network.

    1. Developmental Biology
    2. Neuroscience
    Mariah L Hoye et al.
    Research Article

    Mutations in the RNA helicase, DDX3X, are a leading cause of Intellectual Disability and present as DDX3X syndrome, a neurodevelopmental disorder associated with cortical malformations and autism. Yet, the cellular and molecular mechanisms by which DDX3X controls cortical development are largely unknown. Here, using a mouse model of Ddx3x loss-of-function we demonstrate that DDX3X directs translational and cell cycle control of neural progenitors, which underlies precise corticogenesis. First, we show brain development is sensitive to Ddx3x dosage; complete Ddx3x loss from neural progenitors causes microcephaly in females, whereas hemizygous males and heterozygous females show reduced neurogenesis without marked microcephaly. In addition, Ddx3x loss is sexually dimorphic, as its paralog, Ddx3y, compensates for Ddx3x in the developing male neocortex. Using live imaging of progenitors, we show that DDX3X promotes neuronal generation by regulating both cell cycle duration and neurogenic divisions. Finally, we use ribosome profiling in vivo to discover the repertoire of translated transcripts in neural progenitors, including those which are DDX3X-dependent and essential for neurogenesis. Our study reveals invaluable new insights into the etiology of DDX3X syndrome, implicating dysregulated progenitor cell cycle dynamics and translation as pathogenic mechanisms.