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PXD051022

PXD051022 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleShared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice.
DescriptionDespite 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 three independent models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments - a non-perceptual 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). Proteomic profiling of tissue samples across different brain regions didn't show a perturbation in Kv1 levels in mutant mice. 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 non-developmental source of such deficits in ASD.
HostingRepositoryPRIDE
AnnounceDate2024-05-16
AnnouncementXMLSubmission_2024-05-15_18:59:09.415.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterArmel Nicolas
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF HT
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-03-27 10:12:34ID requested
12024-05-15 18:59:09announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Setd5, superior coliculus, sensorimotor transformation, periaqueductal grey
Contact List
Maximilian Jösch
contact affiliationJösch Group "Neuroethology", ISTA (Institute of Science and Technology Austria), Am Campus 1, Klosterneuburg, Niederösterreich, Austria
contact emailmaxjosch@ist.ac.at
lab head
Armel Nicolas
contact affiliationIST Austria
contact emailarmel.nicolas@ist.ac.at
dataset submitter
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Dataset FTP location
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