Your browser doesn't support javascript.
loading
Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.
Vormstein-Schneider, Douglas; Lin, Jessica D; Pelkey, Kenneth A; Chittajallu, Ramesh; Guo, Baolin; Arias-Garcia, Mario A; Allaway, Kathryn; Sakopoulos, Sofia; Schneider, Gates; Stevenson, Olivia; Vergara, Josselyn; Sharma, Jitendra; Zhang, Qiangge; Franken, Tom P; Smith, Jared; Ibrahim, Leena A; Mastro, Kevin J; Sabri, Ehsan; Huang, Shuhan; Favuzzi, Emilia; Burbridge, Timothy; Xu, Qing; Guo, Lihua; Vogel, Ian; Sanchez, Vanessa; Saldi, Giuseppe A; Gorissen, Bram L; Yuan, Xiaoqing; Zaghloul, Kareem A; Devinsky, Orrin; Sabatini, Bernardo L; Batista-Brito, Renata; Reynolds, John; Feng, Guoping; Fu, Zhanyan; McBain, Chris J; Fishell, Gord; Dimidschstein, Jordane.
Afiliação
  • Vormstein-Schneider D; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Lin JD; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Pelkey KA; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • Chittajallu R; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • Guo B; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Arias-Garcia MA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Allaway K; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Sakopoulos S; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Schneider G; NYU Langone Medical Center, New York University, New York, NY, USA.
  • Stevenson O; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Vergara J; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Sharma J; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Zhang Q; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Franken TP; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Smith J; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Ibrahim LA; Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Mastro KJ; Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA.
  • Sabri E; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Huang S; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Favuzzi E; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Burbridge T; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Xu Q; Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Guo L; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Vogel I; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Sanchez V; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Saldi GA; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Gorissen BL; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Yuan X; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Zaghloul KA; Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE.
  • Devinsky O; Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE.
  • Sabatini BL; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Batista-Brito R; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Reynolds J; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Feng G; Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
  • Fu Z; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • McBain CJ; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
  • Fishell G; National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Dimidschstein J; Comprehensive Epilepsy Center, New York University School of Medicine, New York, NY, USA.
Nat Neurosci ; 23(12): 1629-1636, 2020 12.
Article em En | MEDLINE | ID: mdl-32807948
ABSTRACT
Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dependovirus / Vetores Genéticos / Interneurônios Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dependovirus / Vetores Genéticos / Interneurônios Idioma: En Ano de publicação: 2020 Tipo de documento: Article