1. Neuroscience

DYT1 dystonia increases risk taking in humans

  1. David Arkadir  Is a corresponding author
  2. Angela Radulescu
  3. Deborah Raymond
  4. Naomi Lubarr
  5. Susan B Bressman
  6. Pietro Mazzoni
  7. Yael Niv  Is a corresponding author
  1. Hadassah Medical Center and the Hebrew University, Israel
  2. Princeton University, United States
  3. Beth Israel Medical Center, United States
  4. Columbia University, United States
https://doi.org/10.7554/eLife.14155
Share this article
Cite this article
  1. David Arkadir
  2. Angela Radulescu
  3. Deborah Raymond
  4. Naomi Lubarr
  5. Susan B Bressman
  6. Pietro Mazzoni
  7. Yael Niv
(2016)
DYT1 dystonia increases risk taking in humans
eLife 5:e14155.
https://doi.org/10.7554/eLife.14155
  2. Download BibTeX
  3. Download .RIS

Abstract

It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a single-mutation motor disorder, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans.

Article and author information

Author details

  1. David Arkadir

    Department of Neurology, Hadassah Medical Center, Hadassah Medical Center and the Hebrew University, Jerusalem, Israel
    For correspondence
    arkadir@gmail.com
    Competing interests
    The authors declare that no competing interests exist.

  2. Angela Radulescu

    Psychology Department, Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Deborah Raymond

    Department of Neurology, Beth Israel Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Naomi Lubarr

    Department of Neurology, Beth Israel Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Susan B Bressman

    Department of Neurology, Beth Israel Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Pietro Mazzoni

    The Neurological Institute, Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Yael Niv

    Psychology Department, Princeton Neuroscience Institute, Princeton University, Princeton, United States
    For correspondence
    yael@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Rui M Costa, Fundação Champalimaud, Portugal

Ethics

Human subjects: All participants gave informed consent and the study was approved by the Institutional Review Boards of Columbia University, Beth Israel Medical Center, and Princeton University.

Version history

  1. Received: January 2, 2016
  2. Accepted: May 28, 2016
  3. Accepted Manuscript published: June 1, 2016 (version 1)
  4. Accepted Manuscript updated: June 2, 2016 (version 2)
  5. Version of Record published: July 19, 2016 (version 3)

Copyright

© 2016, Arkadir 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

  • 1,418
    views
  • 335
    downloads
  • 12
    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. David Arkadir
  2. Angela Radulescu
  3. Deborah Raymond
  4. Naomi Lubarr
  5. Susan B Bressman
  6. Pietro Mazzoni
  7. Yael Niv
(2016)
DYT1 dystonia increases risk taking in humans
eLife 5:e14155.
https://doi.org/10.7554/eLife.14155

Share this article

https://doi.org/10.7554/eLife.14155

Categories and tags

Research organism

Further reading

    1. Cell Biology
    2. Neuroscience

    KIS counteracts PTBP2 and regulates alternative exon usage in neurons

    Marcos Moreno-Aguilera, Alba M Neher ... Carme Gallego
    Research Article Updated

    Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.

    1. Genetics and Genomics
    2. Neuroscience

    Genetic Chimerism: Marmosets contain multitudes

    Kenneth Chiou, Noah Snyder-Mackler
    Insight

    Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.

    1. Cell Biology
    2. Neuroscience

    Unraveling the link between Neuropathy Target Esterase NTE/SWS, lysosomal storage diseases, inflammation, abnormal fatty acid metabolism, and leaky brain barrier

    Mariana I Tsap, Andriy S Yatsenko ... Halyna R Shcherbata
    Research Article

    Mutations in Drosophila Swiss Cheese (SWS) gene or its vertebrate orthologue Neuropathy Target Esterase (NTE) lead to progressive neuronal degeneration in flies and humans. Despite its enzymatic function as a phospholipase is well-established, the molecular mechanism responsible for maintaining nervous system integrity remains unclear. In this study, we found that NTE/SWS is present in surface glia that forms the blood-brain-barrier (BBB) and that NTE/SWS is important to maintain its structure and permeability. Importantly, BBB glia-specific expression of Drosophila NTE/SWS or human NTE in the sws mutant background fully rescues surface glial organization and partially restores BBB integrity, suggesting a conserved function of NTE/SWS. Interestingly, sws mutant glia showed abnormal organization of plasma membrane domains and tight junction rafts accompanied by the accumulation of lipid droplets, lysosomes, and multilamellar bodies. Since the observed cellular phenotypes closely resemble the characteristics described in a group of metabolic disorders known as lysosomal storage diseases (LSDs), our data established a novel connection between NTE/SWS and these conditions. We found that mutants with defective BBB exhibit elevated levels of fatty acids, which are precursors of eicosanoids and are involved in the inflammatory response. Also, as a consequence of a permeable BBB, several innate immunity factors are upregulated in an age-dependent manner, while BBB glia-specific expression of NTE/SWS normalizes inflammatory response. Treatment with anti-inflammatory agents prevents the abnormal architecture of the BBB, suggesting that inflammation contributes to the maintenance of a healthy brain barrier. Considering the link between a malfunctioning BBB and various neurodegenerative diseases, gaining a deeper understanding of the molecular mechanisms causing inflammation due to a defective BBB could help to promote the use of anti-inflammatory therapies for age-related neurodegeneration.