---
APC_amount: 6081,83 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '17142'
abstract:
- lang: eng
  text: Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected
    individuals share strikingly similar and correlated behavioural traits that include
    perceptual and sensory processing challenges. Notably, the severity of these sensory
    symptoms is often predictive of the expression of other autistic traits. However,
    the origin of these perceptual deficits remains largely elusive. Here, we show
    a recurrent impairment in visual threat perception that is similarly impaired
    in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly,
    this deficit is associated with reduced avoidance of threatening environments—a
    nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation,
    we define the molecular mechanism. We show that the perceptual impairment is caused
    by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential
    for the initiation of escape responses, the dorsal periaqueductal grey (dPAG).
    Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance
    deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore,
    we show that different molecular mechanisms converge on similar behavioural phenotypes
    by demonstrating that the autism models Cul3 and Ptchd1, despite having similar
    behavioural phenotypes, differ in their functional and molecular alteration. Our
    findings reveal a link between rapid perception controlled by subcortical pathways
    and appropriate learned interactions with the environment and define a nondevelopmental
    source of such deficits in ASD.
acknowledgement: 'This work was supported by a European Research Council Starting
  Grant 756502 (MJ). '
article_number: e3002668
article_processing_charge: Yes
article_type: original
author:
- first_name: Laura
  full_name: Burnett, Laura
  id: 3B717F68-F248-11E8-B48F-1D18A9856A87
  last_name: Burnett
  orcid: 0000-0002-8937-410X
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Olga
  full_name: Symonova, Olga
  id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
  last_name: Symonova
  orcid: 0000-0003-2012-9947
- first_name: Tomas
  full_name: Masson, Tomas
  id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207
  last_name: Masson
  orcid: 0000-0002-2634-6283
- first_name: Tomas A
  full_name: Vega Zuniga, Tomas A
  id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
  last_name: Vega Zuniga
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
citation:
  ama: Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments
    in visual perception and place avoidance across different autism models are driven
    by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. <i>PLoS
    Biology</i>. 2024;22. doi:<a href="https://doi.org/10.1371/journal.pbio.3002668">10.1371/journal.pbio.3002668</a>
  apa: Burnett, L., Koppensteiner, P., Symonova, O., Masson, T., Vega Zuniga, T. A.,
    Contreras, X., … Jösch, M. A. (2024). Shared behavioural impairments in visual
    perception and place avoidance across different autism models are driven by periaqueductal
    grey hypoexcitability in Setd5 haploinsufficient mice. <i>PLoS Biology</i>. Public
    Library of Science. <a href="https://doi.org/10.1371/journal.pbio.3002668">https://doi.org/10.1371/journal.pbio.3002668</a>
  chicago: Burnett, Laura, Peter Koppensteiner, Olga Symonova, Tomas Masson, Tomas
    A Vega Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino,
    and Maximilian A Jösch. “Shared Behavioural Impairments in Visual Perception and
    Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey
    Hypoexcitability in Setd5 Haploinsufficient Mice.” <i>PLoS Biology</i>. Public
    Library of Science, 2024. <a href="https://doi.org/10.1371/journal.pbio.3002668">https://doi.org/10.1371/journal.pbio.3002668</a>.
  ieee: L. Burnett <i>et al.</i>, “Shared behavioural impairments in visual perception
    and place avoidance across different autism models are driven by periaqueductal
    grey hypoexcitability in Setd5 haploinsufficient mice,” <i>PLoS Biology</i>, vol.
    22. Public Library of Science, 2024.
  ista: Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras
    X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments
    in visual perception and place avoidance across different autism models are driven
    by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS
    Biology. 22, e3002668.
  mla: Burnett, Laura, et al. “Shared Behavioural Impairments in Visual Perception
    and Place Avoidance across Different Autism Models Are Driven by Periaqueductal
    Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” <i>PLoS Biology</i>, vol.
    22, e3002668, Public Library of Science, 2024, doi:<a href="https://doi.org/10.1371/journal.pbio.3002668">10.1371/journal.pbio.3002668</a>.
  short: L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X.
    Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, PLoS Biology 22
    (2024).
corr_author: '1'
date_created: 2024-06-16T22:01:05Z
date_published: 2024-06-10T00:00:00Z
date_updated: 2025-09-08T07:57:11Z
day: '10'
ddc:
- '570'
department:
- _id: RySh
- _id: GaNo
- _id: MaJö
doi: 10.1371/journal.pbio.3002668
ec_funded: 1
external_id:
  isi:
  - '001246176800003'
  pmid:
  - '38857283'
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has_accepted_license: '1'
intvolume: '        22'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '756502'
  name: Circuits of Visual Attention
publication: PLoS Biology
publication_identifier:
  eissn:
  - 1545-7885
  issn:
  - 1544-9173
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://doi.org/10.5281/zenodo.11130587
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  - id: '15385'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: Shared behavioural impairments in visual perception and place avoidance across
  different autism models are driven by periaqueductal grey hypoexcitability in Setd5
  haploinsufficient mice
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 22
year: '2024'
...