---
_id: '12716'
abstract:
- lang: eng
text: "The process of detecting and evaluating sensory information to guide behaviour
is termed perceptual decision-making (PDM), and is critical for the ability of
an organism to interact with its external world. Individuals with autism, a neurodevelopmental
condition primarily characterised by social and communication difficulties, frequently
exhibit altered sensory processing and PDM difficulties are widely reported. Recent
technological advancements have pushed forward our understanding of the genetic
changes accompanying this condition, however our understanding of how these mutations
affect the function of specific neuronal circuits and bring about the corresponding
behavioural changes remains limited. Here, we use an innate PDM task, the looming
avoidance response (LAR) paradigm, to identify a convergent behavioural abnormality
across three molecularly distinct genetic mouse models of autism (Cul3, Setd5
and Ptchd1). Although mutant mice can rapidly detect threatening visual stimuli,
their responses are consistently delayed, requiring longer to initiate an appropriate
response than their wild-type siblings. Mutant animals show abnormal adaptation
in both their stimulus- evoked escape responses and exploratory dynamics following
repeated stimulus presentations. Similarly delayed behavioural responses are observed
in wild-type animals when faced with more ambiguous threats, suggesting the mutant
phenotype could arise from a dysfunction in the flexible control of this PDM process.\r\nOur
knowledge of the core neuronal circuitry mediating the LAR facilitated a detailed
dissection of the neuronal mechanisms underlying the behavioural impairment. In
vivo extracellular recording revealed that visual responses were unaffected within
a key brain region for the rapid processing of visual threats, the superior colliculus
(SC), indicating that the behavioural delay was unlikely to originate from sensory
impairments. Delayed behavioural responses were recapitulated in the Setd5 model
following optogenetic stimulation of the excitatory output neurons of the SC,
which are known to mediate escape initiation through the activation of cells in
the underlying dorsal periaqueductal grey (dPAG). In vitro patch-clamp recordings
of dPAG cells uncovered a stark hypoexcitability phenotype in two out of the three
genetic models investigated (Setd5 and Ptchd1), that in Setd5, is mediated by
the misregulation of voltage-gated potassium channels. Overall, our results show
that the ability to use visual information to drive efficient escape responses
is impaired in three diverse genetic mouse models of autism and that, in one of
the models studied, this behavioural delay likely originates from differences
in the intrinsic excitability of a key subcortical node, the dPAG. Furthermore,
this work showcases the use of an innate behavioural paradigm to mechanistically
dissect PDM processes in autism."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: CampIT
alternative_title:
- ISTA Thesis
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
citation:
ama: Burnett L. To flee, or not to flee? Using innate defensive behaviours to investigate
rapid perceptual decision-making through subcortical circuits in mouse models
of autism. 2023. doi:10.15479/at:ista:12716
apa: Burnett, L. (2023). To flee, or not to flee? Using innate defensive behaviours
to investigate rapid perceptual decision-making through subcortical circuits in
mouse models of autism. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12716
chicago: Burnett, Laura. “To Flee, or Not to Flee? Using Innate Defensive Behaviours
to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in
Mouse Models of Autism.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12716.
ieee: L. Burnett, “To flee, or not to flee? Using innate defensive behaviours to
investigate rapid perceptual decision-making through subcortical circuits in mouse
models of autism,” Institute of Science and Technology Austria, 2023.
ista: Burnett L. 2023. To flee, or not to flee? Using innate defensive behaviours
to investigate rapid perceptual decision-making through subcortical circuits in
mouse models of autism. Institute of Science and Technology Austria.
mla: Burnett, Laura. To Flee, or Not to Flee? Using Innate Defensive Behaviours
to Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in
Mouse Models of Autism. Institute of Science and Technology Austria, 2023,
doi:10.15479/at:ista:12716.
short: L. Burnett, To Flee, or Not to Flee? Using Innate Defensive Behaviours to
Investigate Rapid Perceptual Decision-Making through Subcortical Circuits in Mouse
Models of Autism, Institute of Science and Technology Austria, 2023.
date_created: 2023-03-08T15:19:45Z
date_published: 2023-03-10T00:00:00Z
date_updated: 2023-04-05T10:59:04Z
day: '10'
ddc:
- '599'
- '573'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MaJö
doi: 10.15479/at:ista:12716
ec_funded: 1
file:
- access_level: closed
checksum: 6c6d9cc2c4cdacb74e6b1047a34d7332
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: lburnett
date_created: 2023-03-08T15:08:46Z
date_updated: 2023-03-08T15:08:46Z
file_id: '12717'
file_name: Burnett_Thesis_2023.docx
file_size: 23029260
relation: source_file
- access_level: open_access
checksum: cebc77705288bf4382db9b3541483cd0
content_type: application/pdf
creator: lburnett
date_created: 2023-03-08T15:08:46Z
date_updated: 2023-03-08T15:08:46Z
file_id: '12718'
file_name: Burnett_Thesis_2023_pdfA.pdf
file_size: 11959869
relation: main_file
success: 1
file_date_updated: 2023-03-08T15:08:46Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '178'
project:
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '756502'
name: Circuits of Visual Attention
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Maximilian A
full_name: Jösch, Maximilian A
id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
last_name: Jösch
orcid: 0000-0002-3937-1330
title: To flee, or not to flee? Using innate defensive behaviours to investigate rapid
perceptual decision-making through subcortical circuits in mouse models of autism
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...