---
_id: '15385'
abstract:
- lang: eng
text: "Relevant information about the data can be found in the 'Readme_Data.txt'
file. \r\nA previous version of the publication can be found on BioRxiv: https://www.biorxiv.org/content/10.1101/2022.10.11.511691v4\r\nand
published in Plos Biology (2024)"
acknowledged_ssus:
- _id: PreCl
- _id: M-Shop
- _id: LifeSc
- _id: Bio
acknowledgement: 'We thank Armel Nicolas, Bella Bruszel and Ewelina Dutkiewicz from
the ISTA Mass Spectrometry Service (Lab Services Facilities) for all Proteomics
work, including samples preparation, LC/MS data acquisition, searches and data evaluation.
We thank Prof. Peter Jonas for his suggestion on the involvement of potassium channels
and members of the Neuroethology group for their comments on the manuscript. Katalin
Szigeti and Julie Murmann for experimental help. This research was supported by
the Scientific Service Units of ISTA through resources provided by the Lab Support
Facility, the Imaging and Optics Facility, the Machine Shop Unit and the Preclinical
Facility, especially Freyja Langer and Michael Schunn. '
article_processing_charge: No
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. 2024.
doi:10.15479/AT:ISTA:15385
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. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:15385
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.” Institute of Science and Technology
Austria, 2024. https://doi.org/10.15479/AT:ISTA:15385.
ieee: L. Burnett 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.” Institute of Science and
Technology Austria, 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, Institute
of Science and Technology Austria, 10.15479/AT:ISTA:15385.
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. Institute of Science
and Technology Austria, 2024, doi:10.15479/AT:ISTA:15385.
short: L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X.
Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, (2024).
corr_author: '1'
date_created: 2024-05-13T15:04:04Z
date_published: 2024-05-15T00:00:00Z
date_updated: 2025-09-08T07:57:11Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PreCl
- _id: SiHi
- _id: RySh
- _id: GaNo
doi: 10.15479/AT:ISTA:15385
file:
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checksum: 9205eb0876f0f08552dbad80d6884b4b
content_type: application/zip
creator: mjoesch
date_created: 2024-05-15T06:09:17Z
date_updated: 2024-05-15T06:09:17Z
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file_size: '1149617663'
relation: main_file
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creator: mjoesch
date_created: 2024-05-15T06:09:12Z
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file_size: '1335626779'
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date_updated: 2024-05-16T09:08:20Z
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file_size: 18841
relation: main_file
success: 1
file_date_updated: 2024-05-16T09:08:20Z
has_accepted_license: '1'
keyword:
- ASD
- periaqueductal gray
- perception
- behavior
- potassium channels
month: '05'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '17142'
relation: used_in_publication
status: public
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_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: research_data
user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d
year: '2024'
...
---
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. PLoS
Biology. 2024;22. doi:10.1371/journal.pbio.3002668
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. PLoS Biology. Public
Library of Science. https://doi.org/10.1371/journal.pbio.3002668
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.” PLoS Biology. Public
Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002668.
ieee: L. Burnett 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,” PLoS Biology, 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.” PLoS Biology, vol.
22, e3002668, Public Library of Science, 2024, doi:10.1371/journal.pbio.3002668.
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'
file:
- access_level: open_access
checksum: 496e1aa4fd5b92b7e4087ecc2c964133
content_type: application/pdf
creator: dernst
date_created: 2025-01-09T10:39:41Z
date_updated: 2025-01-09T10:39:41Z
file_id: '18805'
file_name: 2024_PloS_Burnett.pdf
file_size: 4016568
relation: main_file
success: 1
file_date_updated: 2025-01-09T10:39:41Z
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
record:
- 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'
...
---
_id: '15268'
abstract:
- lang: eng
text: Apolipoprotein A‐I (apoA‐I) has a key function in the reverse cholesterol
transport. However, aggregation of apoA‐I single point mutants can lead to hereditary
amyloid pathology. Although several studies have tackled the biophysical and structural
consequences introduced by these mutations, there is little information addressing
the relationship between the evolutionary and structural features that contribute
to the amyloid behavior of apoA‐I. We combined evolutionary studies, in silico
mutagenesis and molecular dynamics (MD) simulations to provide a comprehensive
analysis of the conservation and pathogenic role of the aggregation‐prone regions
(APRs) present in apoA‐I. Sequence analysis demonstrated that among the four amyloidogenic
regions described for human apoA‐I, only two (APR1 and APR4) are evolutionary
conserved across different species of Sarcopterygii. Moreover, stability analysis
carried out with the FoldX engine showed that APR1 contributes to the marginal
stability of apoA‐I. Structural properties of full‐length apoA‐I models suggest
that aggregation is avoided by placing APRs into highly packed and rigid portions
of its native fold. Compared to silent variants extracted from the gnomAD database,
the thermodynamic and pathogenic impact of amyloid mutations showed evidence of
a higher destabilizing effect. MD simulations of the amyloid variant G26R evidenced
the partial unfolding of the alpha‐helix bundle with the concomitant exposure
of APR1 to the solvent, suggesting an insight into the early steps involved in
its aggregation. Our findings highlight APR1 as a relevant component for apoA‐I
structural integrity and emphasize a destabilizing effect of amyloid variants
that leads to the exposure of this region.
article_processing_charge: No
article_type: original
author:
- first_name: Romina A.
full_name: Gisonno, Romina A.
last_name: Gisonno
- first_name: Tomas
full_name: Masson, Tomas
id: 93ac43e8-8599-11eb-9b86-f6efb0a4c207
last_name: Masson
orcid: 0000-0002-2634-6283
- first_name: Nahuel A.
full_name: Ramella, Nahuel A.
last_name: Ramella
- first_name: Exequiel E.
full_name: Barrera, Exequiel E.
last_name: Barrera
- first_name: Víctor
full_name: Romanowski, Víctor
last_name: Romanowski
- first_name: M. Alejandra
full_name: Tricerri, M. Alejandra
last_name: Tricerri
citation:
ama: 'Gisonno RA, Masson T, Ramella NA, Barrera EE, Romanowski V, Tricerri MA. Evolutionary
and structural constraints influencing apolipoprotein A‐I amyloid behavior. Proteins:
Structure, Function, and Bioinformatics. 2022;90(1):258-269. doi:10.1002/prot.26217'
apa: 'Gisonno, R. A., Masson, T., Ramella, N. A., Barrera, E. E., Romanowski, V.,
& Tricerri, M. A. (2022). Evolutionary and structural constraints influencing
apolipoprotein A‐I amyloid behavior. Proteins: Structure, Function, and Bioinformatics.
Wiley. https://doi.org/10.1002/prot.26217'
chicago: 'Gisonno, Romina A., Tomas Masson, Nahuel A. Ramella, Exequiel E. Barrera,
Víctor Romanowski, and M. Alejandra Tricerri. “Evolutionary and Structural Constraints
Influencing Apolipoprotein A‐I Amyloid Behavior.” Proteins: Structure, Function,
and Bioinformatics. Wiley, 2022. https://doi.org/10.1002/prot.26217.'
ieee: 'R. A. Gisonno, T. Masson, N. A. Ramella, E. E. Barrera, V. Romanowski, and
M. A. Tricerri, “Evolutionary and structural constraints influencing apolipoprotein
A‐I amyloid behavior,” Proteins: Structure, Function, and Bioinformatics,
vol. 90, no. 1. Wiley, pp. 258–269, 2022.'
ista: 'Gisonno RA, Masson T, Ramella NA, Barrera EE, Romanowski V, Tricerri MA.
2022. Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid
behavior. Proteins: Structure, Function, and Bioinformatics. 90(1), 258–269.'
mla: 'Gisonno, Romina A., et al. “Evolutionary and Structural Constraints Influencing
Apolipoprotein A‐I Amyloid Behavior.” Proteins: Structure, Function, and Bioinformatics,
vol. 90, no. 1, Wiley, 2022, pp. 258–69, doi:10.1002/prot.26217.'
short: 'R.A. Gisonno, T. Masson, N.A. Ramella, E.E. Barrera, V. Romanowski, M.A.
Tricerri, Proteins: Structure, Function, and Bioinformatics 90 (2022) 258–269.'
corr_author: '1'
date_created: 2024-04-03T07:49:53Z
date_published: 2022-01-01T00:00:00Z
date_updated: 2024-10-09T21:08:44Z
day: '01'
department:
- _id: MaJö
doi: 10.1002/prot.26217
external_id:
pmid:
- '34414600'
intvolume: ' 90'
issue: '1'
keyword:
- Molecular Biology
- Biochemistry
- Structural Biology
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.09.18.304337
month: '01'
oa: 1
oa_version: Preprint
page: 258-269
pmid: 1
publication: 'Proteins: Structure, Function, and Bioinformatics'
publication_identifier:
eissn:
- 1097-0134
issn:
- 0887-3585
publication_status: published
publisher: Wiley
quality_controlled: '1'
status: public
title: Evolutionary and structural constraints influencing apolipoprotein A‐I amyloid
behavior
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 90
year: '2022'
...