Synaptic and intrinsic mechanisms underlying development of cortical direction selectivity

Abstract

Modifications of synaptic inputs and cell-intrinsic properties both contribute to neuronal plasticity and development. To better understand these mechanisms, we undertook an intracellular analysis of the development of direction selectivity in the ferret visual cortex, which occurs rapidly over a few days after eye opening. We found strong evidence of developmental changes in linear spatiotemporal receptive fields of simple cells, implying alterations in circuit inputs. Further, this receptive field plasticity was accompanied by increases in near-spike-threshold excitability and input-output gain that resulted in dramatically increased spiking responses in the experienced state. Increases in subthreshold membrane responses induced by the receptive field plasticity and the increased input-output spiking gain were both necessary to explain the elevated firing rates in experienced ferrets. These results demonstrate that cortical direction selectivity develops through a combination of plasticity in inputs and in cell-intrinsic properties.

Data availability

Data is available at our website at http://data.vhlab.org. Code is available at http://code.vhlab.org (links to GitHub).

Article and author information

Author details

  1. Arani Roy

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jason J Osik

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Benyamin Meschede-Krasa

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Wesley T Alford

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel P Leman

    Department of Biology, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Stephen D Van Hooser

    Department of Biology, Brandeis University, Waltham, United States
    For correspondence
    vanhoosr@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1112-5832

Funding

National Eye Institute (EY022122)

  • Arani Roy
  • Jason J Osik
  • Benyamin Meschede-Krasa
  • Wesley T Alford
  • Daniel P Leman
  • Stephen D Van Hooser

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of Brandeis University (19010, 16003, 13011). All procedures were performed under isoflurane anesthesia and every effort was made to minimize suffering.

Reviewing Editor

  1. Marla B Feller, University of California, Berkeley, United States

Version history

  1. Received: May 2, 2020
  2. Accepted: July 23, 2020
  3. Accepted Manuscript published: July 23, 2020 (version 1)
  4. Version of Record published: August 20, 2020 (version 2)

Copyright

© 2020, Roy 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

  • 1,848
    Page views
  • 226
    Downloads
  • 7
    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. Arani Roy
  2. Jason J Osik
  3. Benyamin Meschede-Krasa
  4. Wesley T Alford
  5. Daniel P Leman
  6. Stephen D Van Hooser
(2020)
Synaptic and intrinsic mechanisms underlying development of cortical direction selectivity
eLife 9:e58509.
https://doi.org/10.7554/eLife.58509

Share this article

https://doi.org/10.7554/eLife.58509

Further reading

    1. Biochemistry and Chemical Biology
    2. Developmental Biology
    Sima Stroganov, Talia Harris ... Michal Neeman
    Research Article Updated

    Background:

    Fetal growth restriction (FGR) is a pregnancy complication in which a newborn fails to achieve its growth potential, increasing the risk of perinatal morbidity and mortality. Chronic maternal gestational hypoxia, as well as placental insufficiency are associated with increased FGR incidence; however, the molecular mechanisms underlying FGR remain unknown.

    Methods:

    Pregnant mice were subjected to acute or chronic hypoxia (12.5% O2) resulting in reduced fetal weight. Placenta oxygen transport was assessed by blood oxygenation level dependent (BOLD) contrast magnetic resonance imaging (MRI). The placentae were analyzed via immunohistochemistry and in situ hybridization. Human placentae were selected from FGR and matched controls and analyzed by immunohistochemistry (IHC). Maternal and cord sera were analyzed by mass spectrometry.

    Results:

    We show that murine acute and chronic gestational hypoxia recapitulates FGR phenotype and affects placental structure and morphology. Gestational hypoxia decreased labyrinth area, increased the incidence of red blood cells (RBCs) in the labyrinth while expanding the placental spiral arteries (SpA) diameter. Hypoxic placentae exhibited higher hemoglobin-oxygen affinity compared to the control. Placental abundance of Bisphosphoglycerate mutase (BPGM) was upregulated in the syncytiotrophoblast and spiral artery trophoblast cells (SpA TGCs) in the murine gestational hypoxia groups compared to the control. Hif1α levels were higher in the acute hypoxia group compared to the control. In contrast, human FGR placentae exhibited reduced BPGM levels in the syncytiotrophoblast layer compared to placentae from healthy uncomplicated pregnancies. Levels of 2,3 BPG, the product of BPGM, were lower in cord serum of human FGR placentae compared to control. Polar expression of BPGM was found in both human and mouse placentae syncytiotrophoblast, with higher expression facing the maternal circulation. Moreover, in the murine SpA TGCs expression of BPGM was concentrated exclusively in the apical cell side, in direct proximity to the maternal circulation.

    Conclusions:

    This study suggests a possible involvement of placental BPGM in maternal-fetal oxygen transfer, and in the pathophysiology of FGR.

    Funding:

    This work was supported by the Weizmann Krenter Foundation and the Weizmann – Ichilov (Tel Aviv Sourasky Medical Center) Collaborative Grant in Biomedical Research, by the Minerva Foundation, by the ISF KillCorona grant 3777/19.

    1. Developmental Biology
    2. Neuroscience
    Simon Desiderio, Frederick Schwaller ... Frederic Marmigere
    Research Article

    Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.