Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Viral manipulation of functionally distinct neurons from mice to humans

DC Vormstein-Schneider, JD Lin, KA Pelkey, R Chittajallu, B Guo, M Arias Garcia, S Sakopoulos, O Stevenson, G Schneider, Q Zhang, J Sharma, TP Franken, J Smith, I Vogel, V Sanchez, LA Ibrahim, T Burbridge, E Favuzzi, GA Saldi, Q Xu, L Guo, X Yuan, KA Zaghloul, E Sabri, EM Goldberg, O Devinsky, R Batista-Brito, J Reynolds, G Feng, Z Fu, CJ McBain, GJ Fishell, J Dimidschstein
doi: https://doi.org/10.1101/808170
DC Vormstein-Schneider
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JD Lin
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KA Pelkey
4Cellular and Synaptic Physiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R Chittajallu
4Cellular and Synaptic Physiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B Guo
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M Arias Garcia
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S Sakopoulos
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
O Stevenson
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Schneider
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Q Zhang
6McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Sharma
6McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TP Franken
7Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Smith
7Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
I Vogel
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V Sanchez
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
LA Ibrahim
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
2Department of Neurobiology at Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T Burbridge
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
2Department of Neurobiology at Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Favuzzi
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
2Department of Neurobiology at Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
GA Saldi
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
3Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Q Xu
3Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L Guo
3Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
X Yuan
4Cellular and Synaptic Physiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KA Zaghloul
5Surgical Neurology, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
E Sabri
9Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
EM Goldberg
10Department of Neuroscience, The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
O Devinsky
8Comprehensive Epilepsy Center, New York University School of Medicine, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R Batista-Brito
9Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Reynolds
7Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
G Feng
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
6McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Z Fu
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
CJ McBain
4Cellular and Synaptic Physiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
GJ Fishell
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
2Department of Neurobiology at Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J Dimidschstein
1Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jordane@broadinstitute.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Recent success in identifying gene regulatory elements in the context of recombinant adeno-associated virus vectors have enabled cell type-restricted gene expression. However, within the cerebral cortex these tools are presently limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple novel enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we identified enhancers that target the breadth of its expression, including two selective for parvalbumin and vasoactive intestinal peptide cortical interneurons. Demonstrating the functional utility of these elements, we found that the PV-specific enhancer allowed for the selective targeting and manipulation of fast-spiking cortical interneurons across species, from mice to humans.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted October 18, 2019.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Viral manipulation of functionally distinct neurons from mice to humans
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Viral manipulation of functionally distinct neurons from mice to humans
DC Vormstein-Schneider, JD Lin, KA Pelkey, R Chittajallu, B Guo, M Arias Garcia, S Sakopoulos, O Stevenson, G Schneider, Q Zhang, J Sharma, TP Franken, J Smith, I Vogel, V Sanchez, LA Ibrahim, T Burbridge, E Favuzzi, GA Saldi, Q Xu, L Guo, X Yuan, KA Zaghloul, E Sabri, EM Goldberg, O Devinsky, R Batista-Brito, J Reynolds, G Feng, Z Fu, CJ McBain, GJ Fishell, J Dimidschstein
bioRxiv 808170; doi: https://doi.org/10.1101/808170
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Viral manipulation of functionally distinct neurons from mice to humans
DC Vormstein-Schneider, JD Lin, KA Pelkey, R Chittajallu, B Guo, M Arias Garcia, S Sakopoulos, O Stevenson, G Schneider, Q Zhang, J Sharma, TP Franken, J Smith, I Vogel, V Sanchez, LA Ibrahim, T Burbridge, E Favuzzi, GA Saldi, Q Xu, L Guo, X Yuan, KA Zaghloul, E Sabri, EM Goldberg, O Devinsky, R Batista-Brito, J Reynolds, G Feng, Z Fu, CJ McBain, GJ Fishell, J Dimidschstein
bioRxiv 808170; doi: https://doi.org/10.1101/808170

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (3504)
  • Biochemistry (7346)
  • Bioengineering (5321)
  • Bioinformatics (20259)
  • Biophysics (10013)
  • Cancer Biology (7742)
  • Cell Biology (11298)
  • Clinical Trials (138)
  • Developmental Biology (6437)
  • Ecology (9950)
  • Epidemiology (2065)
  • Evolutionary Biology (13318)
  • Genetics (9360)
  • Genomics (12581)
  • Immunology (7700)
  • Microbiology (19016)
  • Molecular Biology (7439)
  • Neuroscience (41029)
  • Paleontology (300)
  • Pathology (1229)
  • Pharmacology and Toxicology (2135)
  • Physiology (3157)
  • Plant Biology (6860)
  • Scientific Communication and Education (1272)
  • Synthetic Biology (1895)
  • Systems Biology (5311)
  • Zoology (1089)