1. Neuroscience
Download icon

Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

  1. Marta Maltese
  2. Jennifer Stanic
  3. Annalisa Tassone
  4. Giuseppe Sciamanna
  5. Giulia Ponterio
  6. Valentina Vanni
  7. Giuseppina Martella
  8. Paola Imbriani
  9. Paola Bonsi
  10. Nicola Biagio Mercuri
  11. Fabrizio Gardoni
  12. Antonio Pisani  Is a corresponding author
  1. University of Rome Tor Vergata, Italy
  2. University of Milan, Italy
  3. Fondazione Santa Lucia IRCCS, Italy
Research Article
  • Cited 16
  • Views 1,367
  • Annotations
Cite this article as: eLife 2018;7:e33331 doi: 10.7554/eLife.33331

Abstract

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, though it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers.

Article and author information

Author details

  1. Marta Maltese

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  2. Jennifer Stanic

    Department of Pharmacology, University of Milan, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.

  3. Annalisa Tassone

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  4. Giuseppe Sciamanna

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  5. Giulia Ponterio

    Lab Neurophysiology and Plasticity, Fondazione Santa Lucia IRCCS, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  6. Valentina Vanni

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  7. Giuseppina Martella

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  8. Paola Imbriani

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3373-5073

  9. Paola Bonsi

    Lab Neurophysiology and Plasticity, Fondazione Santa Lucia IRCCS, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5940-9028

  10. Nicola Biagio Mercuri

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    Competing interests
    The authors declare that no competing interests exist.

  11. Fabrizio Gardoni

    Department of Pharmacology, University of Milan, Milan, Italy
    Competing interests
    The authors declare that no competing interests exist.

  12. Antonio Pisani

    Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
    For correspondence
    pisani@uniroma2.it
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8432-594X

Funding

Ministero dell'Istruzione, dell'Università e della Ricerca (PRIN 2010-2011)

  • Antonio Pisani

Ministero dell'Istruzione, dell'Università e della Ricerca (PRIN 2010-2011)

  • Fabrizio Gardoni

Dystonia Medical Research Foundation (2017)

  • Antonio Pisani

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

Ethics

Animal experimentation: Animal breeding and handling were performed in accordance with the guidelines for the use of animals in biomedical research provided by the European Union's directives and Italian laws (2010/63EU, D.lgs. 26/2014; 406 86/609/CEE, D.Lgs 116/1992). The experimental procedures were approved by Fondazione Santa Lucia and University Tor Vergata Animal Care and Use Committees and the Italian Ministry of Health (authorization #223/2017-PR).

Reviewing Editor

  1. Christian Rosenmund, Charité-Universitätsmedizin Berlin, Germany

Publication history

  1. Received: November 3, 2017
  2. Accepted: March 2, 2018
  3. Accepted Manuscript published: March 5, 2018 (version 1)
  4. Version of Record published: March 13, 2018 (version 2)

Copyright

© 2018, Maltese 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

  • 1,367
    Page views
  • 252
    Downloads
  • 16
    Citations

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

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Amplitude modulations of cortical sensory responses in pulsatile evidence accumulation

    Sue Ann Koay et al.
    Research Article Updated

    How does the brain internally represent a sequence of sensory information that jointly drives a decision-making behavior? Studies of perceptual decision-making have often assumed that sensory cortices provide noisy but otherwise veridical sensory inputs to downstream processes that accumulate and drive decisions. However, sensory processing in even the earliest sensory cortices can be systematically modified by various external and internal contexts. We recorded from neuronal populations across posterior cortex as mice performed a navigational decision-making task based on accumulating randomly timed pulses of visual evidence. Even in V1, only a small fraction of active neurons had sensory-like responses time-locked to each pulse. Here, we focus on how these ‘cue-locked’ neurons exhibited a variety of amplitude modulations from sensory to cognitive, notably by choice and accumulated evidence. These task-related modulations affected a large fraction of cue-locked neurons across posterior cortex, suggesting that future models of behavior should account for such influences.

    1. Neuroscience

    Brain functional networks associated with social bonding in monogamous voles

    María Fernanda López-Gutiérrez et al.
    Research Article

    Previous studies have related pair bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially-relevant regions have yet to be described. In this study, we used resting state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair bonding. Thirty-two male and female prairie voles were scanned at baseline, 24h and 2 weeks after the onset of cohabitation By using network based statistics, we identified that the functional connectivity of a cortico-striatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

    1. Developmental Biology
    2. Neuroscience

    Dentate gyrus development requires a cortical hem-derived astrocytic scaffold

    Alessia Caramello et al.
    Research Article Updated

    During embryonic development, radial glial cells give rise to neurons, then to astrocytes following the gliogenic switch. Timely regulation of the switch, operated by several transcription factors, is fundamental for allowing coordinated interactions between neurons and glia. We deleted the gene for one such factor, SOX9, early during mouse brain development and observed a significantly compromised dentate gyrus (DG). We dissected the origin of the defect, targeting embryonic Sox9 deletion to either the DG neuronal progenitor domain or the adjacent cortical hem (CH). We identified in the latter previously uncharacterized ALDH1L1+ astrocytic progenitors, which form a fimbrial-specific glial scaffold necessary for neuronal progenitor migration toward the developing DG. Our results highlight an early crucial role of SOX9 for DG development through regulation of astroglial potential acquisition in the CH. Moreover, we illustrate how formation of a local network, amidst astrocytic and neuronal progenitors originating from adjacent domains, underlays brain morphogenesis.