Titel (eng)

Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice

Autor*in

Laura E. Burnett   Institute of Science and Technology Austria

Maximilian Joesch   Institute of Science and Technology Austria

Gaia Novarino   Institute of Science and Technology Austria

Ryuichi Shigemoto   Institute of Science and Technology Austria

Thomas Rülicke   University of Veterinary Medicine Vienna

Ximena Contreras   Institute of Science and Technology Austria

Tomas Vega-Zuniga   Institute of Science and Technology Austria

Tomás Masson   Institute of Science and Technology Austria

Olga Symonova   Institute of Science and Technology Austria

Peter Koppensteiner   Institute of Science and Technology Austria

Verlag

Public Library of Science

Beschreibung (eng)

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.

Sprache des Objekts

Englisch

Datum

2024

Rechte

Dieses Werk bzw. dieser Inhalt steht unter einer
CC BY 4.0 - Creative Commons Namensnennung 4.0 International Lizenz.

CC BY 4.0 International

http://creativecommons.org/licenses/by/4.0/

Klassifikation

Keywords: Animals; Disease Models, Animal; Mice; Visual Perceptionphysiology; Haploinsufficiencygenetics; Avoidance Learningphysiology; Autism Spectrum Disordergeneticsphysiopathology; Male; Behavior, Animalphysiology; Mice, Inbred C57BL; Histone-Lysine N-Methyltransferasegeneticsmetabolism; Autistic Disordergeneticsphysiopathology

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