Mattis-et-al-2022/datacite.yml

# Metadata for DOI registration according to DataCite Metadata Schema 4.1.
# For detailed schema description see https://doi.org/10.5438/0014

## Required fields

# The main researchers involved. Include digital identifier (e.g., ORCID)
# if possible, including the prefix to indicate its type.
authors:
  -
    firstname: "Joanna"
    lastname: "Mattis"
    affiliation: "The University of Pennsylvania School of Medicine"
  -
    firstname: "Ala"
    lastname: "Somarowthu"
    affiliation: "The Children's Hospital of Philadelphia"
  -
    firstname: "Ethan"
    lastname: "Goldberg"
    affiliation: "The Children's Hospital of Philadelphia"
    id: "ORCID:0000-0002-7404-735X"

# A title to describe the published resource.
title: "Mattis-et-al-2022 Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome"

# Additional information about the resource, e.g., a brief abstract.
description: | 

Accompanying source data to preprint: Mattis, J., et al. Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome.

Dravet syndrome (DS) is a neurodevelopmental disorder due to pathogenic variants in SCN1A encoding the Nav1.1 sodium channel subunit, characterized by treatment-resistant epilepsy, temperature-sensitive seizures, developmental delay/intellectual disability with features of autism spectrum disorder, and increased risk of sudden death. Convergent data suggest hippocampal dentate gyrus (DG) pathology in DS (Scn1a+/-) mice. We performed two-photon calcium imaging in brain slice to uncover a profound dysfunction of filtering of perforant path input by DG in young adult Scn1a+/- mice. This was not due to dysfunction of DG parvalbumin inhibitory interneurons (PV-INs), which were only mildly impaired at this timepoint; however, we identified enhanced excitatory input to granule cells, suggesting that circuit dysfunction is due to excessive excitation rather than impaired inhibition. We confirmed that both optogenetic stimulation of entorhinal cortex and selective chemogenetic inhibition of DG PV-INs lowered seizure threshold in vivo in young adult Scn1a+/- mice. Optogenetic activation of PV-INs, on the other hand, normalized evoked responses in granule cells in vitro. These results establish the corticohippocampal circuit as a key locus of pathology in Scn1a+/- mice and suggest that PV-INs retain powerfu
l inhibitory function and may be harnessed as a potential therapeutic approach towards seizure modulation.

# Lit of keywords the resource should be associated with.
# Give as many keywords as possible, to make the resource findable.
keywords:
  - Dravet syndrome
  - SCN1A
  - Epilepsy
  - Dentate gyrus
  - Optogenetics
  - Two-photon imaging

# License information for this resource. Please provide the license name and/or a link to the license.
# Please add also a corresponding LICENSE file to the repository.
license:
  name: "Creative Commons CC0 1.0 Public Domain Dedication"
  url: "https://creativecommons.org/publicdomain/zero/1.0/"



## Optional Fields

# Funding information for this resource.
# Separate funder name and grant number by comma.
funding:
  - "NIH NINDS, Research Education Grant (R25)"
  - "NIH NINDS, K08 NS121464"
  - "Dravet Syndrome Foundation, Postdoctoral Fellowship Award"
  - "NIH NINDS, K08 NS097633"
  - "NIH NINDS, R01 NS110869"
  - "The Dana Foundation, David Mahoney Neuroimaging Program"
  - "Burroughs Wellcome Fund, Career Award for Medical Scientists"


# Related publications. reftype might be: IsSupplementTo, IsDescribedBy, IsReferencedBy.
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# In the citation field, please provide the full reference, including title, authors, journal etc.
references:
  -
    id: "doi:https://doi.org/10.1101/2021.05.01.442271"
    reftype: "IsSupplementTo"
    citation: "Mattis J, Somarowthu A, Goff KM, Yom J, Sotuyo NP, Mcgarry LM, Feng H, Kaneko K, Goldberg EM. Corticohippocampal circuit dysfunction in a mouse model of Dravet syndrome. 2021.05.01.442271 https://www.biorxiv.org/content/10.1101/2021.05.01.442271v1 (2021) doi:10.1101/2021.05.01.442271."


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resourcetype: Dataset

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templateversion: 1.2