Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

Animals Callithrix Cerebral Cortex / cytology Dependovirus / genetics Female Genetic Vectors / genetics Humans Interneurons / physiology Macaca mulatta Mice Mice, Inbred C57BL NAV1.1 Voltage-Gated Sodium Channel / genetics Neurons Parvalbumins / physiology Rats Rats, Sprague-Dawley Species Specificity Vasoactive Intestinal Peptide / physiology

Journal

Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671

Informations de publication

Date de publication:
12 2020
Historique:
received: 20 12 2019
accepted: 10 07 2020
pubmed: 19 8 2020
medline: 9 2 2021
entrez: 19 8 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41593-020-0692-9 PMID: 32807948 PMC: PMC8015416
pubmed: 32807948
doi: 10.1038/s41593-020-0692-9
pii: 10.1038/s41593-020-0692-9
pmc: PMC8015416
mid: NIHMS1682740
doi:

Substances chimiques

NAV1.1 Voltage-Gated Sodium Channel 0
Parvalbumins 0
Scn1a protein, mouse 0
Vasoactive Intestinal Peptide 37221-79-7

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1629-1636

Subventions

Organisme : NINDS NIH HHS
ID : P01 NS074972
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS046579
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH094271
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH071679
Pays : United States
Organisme : NIMH NIH HHS
ID : UG3 MH120096
Pays : United States
Organisme : NIMH NIH HHS
ID : R37 MH071679
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS081297
Pays : United States
Organisme : NINDS NIH HHS
ID : K99 NS106528
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH111529
Pays : United States

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

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Auteurs

Douglas Vormstein-Schneider (D)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0002-0345-2470

Jessica D Lin (JD)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0002-4093-0005

Kenneth A Pelkey (KA)

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Ramesh Chittajallu (R)

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Baolin Guo (B)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0001-7309-5774

Mario A Arias-Garcia (MA)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Kathryn Allaway (K)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
NYU Langone Medical Center, New York University, New York, NY, USA.

Sofia Sakopoulos (S)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Gates Schneider (G)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Olivia Stevenson (O)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Josselyn Vergara (J)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Jitendra Sharma (J)

McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

Qiangge Zhang (Q)

McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.

Tom P Franken (TP)

Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA.
ORCID: 0000-0001-7160-5152

Jared Smith (J)

Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA.
ORCID: 0000-0002-0273-4898

Leena A Ibrahim (LA)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-8255-3423

Kevin J Mastro (KJ)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Ehsan Sabri (E)

Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.

Shuhan Huang (S)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-3139-7296

Emilia Favuzzi (E)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Timothy Burbridge (T)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Qing Xu (Q)

Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE.

Lihua Guo (L)

Center for Genomics & Systems Biology, New York University, Abu Dhabi, UAE.

Ian Vogel (I)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.

Vanessa Sanchez (V)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0001-9380-5358

Giuseppe A Saldi (GA)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Bram L Gorissen (BL)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0001-5992-0432

Xiaoqing Yuan (X)

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Kareem A Zaghloul (KA)

National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0001-8575-3578

Orrin Devinsky (O)

Comprehensive Epilepsy Center, New York University School of Medicine, New York, NY, USA.
ORCID: 0000-0003-0044-4632

Bernardo L Sabatini (BL)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-0095-9177

Renata Batista-Brito (R)

Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.

John Reynolds (J)

Systems Neurobiology Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA.

Guoping Feng (G)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
ORCID: 0000-0002-8021-277X

Zhanyan Fu (Z)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
ORCID: 0000-0001-9473-2402

Chris J McBain (CJ)

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
ORCID: 0000-0002-5909-0157

Gord Fishell (G)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA, USA.

Jordane Dimidschstein (J)

Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA. jordane@broadinstitute.org.
ORCID: 0000-0001-6289-6891

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Platyrrhini › Cebidae › Callitrichinae › Callithrix › Viral manipulation of functionally distinct...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Viral manipulation of functionally distinct...
questionsmedicales.fr › Virus › Virus à ADN › Parvoviridae › Parvovirinae › Dependovirus › Viral manipulation of functionally distinct...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Vecteurs génétiques › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Viral manipulation of functionally distinct...
questionsmedicales.fr › Cellules › Neurones › Interneurones › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca › Macaca mulatta › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Viral manipulation of functionally distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Canaux sodiques voltage-dépendants › Canal sodique voltage-dépendant NAV1.1 › Viral manipulation of functionally distinct...
questionsmedicales.fr › Cellules › Neurones › Viral manipulation of functionally distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines contractiles › Protéines du muscle › Parvalbumines › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Viral manipulation of functionally distinct...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › Viral manipulation of functionally distinct...
questionsmedicales.fr › Phénomènes biologiques › Spécificité d'espèce › Viral manipulation of functionally distinct...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Neuropeptides › Peptide vasoactif intestinal › Viral manipulation of functionally distinct...