Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory

R J Taugher-Hebl; A Berns; M Jones; A Townsend; A K Eagen; Sarah L Ferri; D R Langbehn; H Janouschek

doi:10.1002/aur.70034

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Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory

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Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory

R J Taugher-Hebl, A Berns, M Jones, A Townsend, A K Eagen, Sarah L Ferri, D R Langbehn and H Janouschek

Autism research, Vol.18(5), pp.1011-1023

05/2025

DOI: 10.1002/aur.70034

PMCID: PMC12123174

PMID: 40247148

Appears in UI Libraries Support Open Access

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Abstract

The contactin-associated protein-like 2 (Cntnap2) gene is relevant to autism spectrum disorder (ASD), which is associated with age-specific structural alterations in limbic brain regions. The Cntnap2 gene encodes for the contactin-associated protein-like 2 (CASPR2) protein, and CASPR2 protein levels are high in the amygdala, a limbic region that is essential for the processing of fear and anxiety. In humans, reduced levels of this protein arising from CNTNAP2 mutations could potentially account for the autism-associated increase in fear and anxiety. Here, we report the extent to which loss of CASPR2 in mice contributes to the development of fear- and anxiety-related behaviors. Pavlovian fear conditioning experiments revealed that loss of CASPR2 has age-dependent effects on the acquisition of fear memory, recall of both cue-evoked and context-related fear memory, and stability of cue-evoked fear memory. Additionally, data from the elevated zero maze suggest that CASPR2 deficiency contributes to anxiety-related behaviors, especially in juvenile (29-day old) mice. These are the first reports of age-dependent effects of CASPR2 deficiency on fear and anxiety-related behaviors, and they set the stage for a better understanding of developmental alterations of fear and anxiety in ASD.

anxiety

Cntnap2

development

fear conditioning

memory

CASPR2

autism spectrum disorder

fear

UIOWA OA Agreement

Details

Title: Subtitle: Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory
Creators: R J Taugher-Hebl - Department of Veterans Affairs Medical Center, Iowa City, Iowa, USA
A Berns - University of Iowa, Neuroscience and Pharmacology
M Jones - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
A Townsend - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
A K Eagen - Department of Psychiatry, Iowa Neuroscience Institute, University of Iowa, Iowa City, Iowa, USA
Sarah L Ferri - University of Iowa
D R Langbehn - University of Iowa
H Janouschek - Department of Psychiatry, Iowa Neuroscience Institute, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Autism research, Vol.18(5), pp.1011-1023
DOI: 10.1002/aur.70034
PMID: 40247148
PMCID: PMC12123174
NLM abbreviation: Autism Res
ISSN: 1939-3806
eISSN: 1939-3806
Publisher: Wiley; HOBOKEN
Grant note: Iowa Neuroscience Institute
Language: English
Electronic publication date: 04/17/2025
Date published: 05/2025
Academic Unit: Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Developmental and Behavioral Pediatrics; Neuroscience and Pharmacology
Record Identifier: 9984811223802771

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