Neuroanatomical Alterations in the CNTNAP2 Mouse Model of Autism Spectrum Disorder

Autism spectrum disorder (ASD) is associated with neurodevelopmental alterations, including atypical forebrain cellular organization. Mutations in several ASD-related genes often result in cerebral cortical anomalies, such as the abnormal developmental migration of excitatory pyramidal cells and the...

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Bibliographic Details
Published in:Brain sciences 2023-05, Vol.13 (6), p.891
Main Authors: Gandhi, Tanya, Canepa, Cade R, Adeyelu, Tolulope T, Adeniyi, Philip A, Lee, Charles C
Format: Article
Language:English
Subjects:
Analysis
Anatomy
Autism
Behavior
Brain
Cell migration
CNTNAP2
CNTNAP2 gene
corticothalamic
Forebrain
Genes
Genetic aspects
Interneurons
Laboratories
Mutants
Mutation
Neural networks
Neurons
Oxidative stress
Parvalbumin
Perineuronal nets
Pyramidal cells
Sensory neurons
Thalamic nuclei
Thalamus
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Summary:Autism spectrum disorder (ASD) is associated with neurodevelopmental alterations, including atypical forebrain cellular organization. Mutations in several ASD-related genes often result in cerebral cortical anomalies, such as the abnormal developmental migration of excitatory pyramidal cells and the malformation of inhibitory neuronal circuitry. Notably here, mutations in the CNTNAP2 gene result in ectopic superficial cortical neurons stalled in lower cortical layers and alterations to the balance of cortical excitation and inhibition. However, the broader circuit-level implications of these findings have not been previously investigated. Therefore, we assessed whether ectopic cortical neurons in CNTNAP2 mutant mice form aberrant connections with higher-order thalamic nuclei, potentially accounting for some autistic behaviors, such as repetitive and hyperactive behaviors. Furthermore, we assessed whether the development of parvalbumin-positive (PV) cortical interneurons and their specialized matrix support structures, called perineuronal nets (PNNs), were altered in these mutant mice. We found alterations in both ectopic neuronal connectivity and in the development of PNNs, PV neurons and PNNs enwrapping PV neurons in various sensory cortical regions and at different postnatal ages in the CNTNAP2 mutant mice, which likely lead to some of the cortical excitation/inhibition (E/I) imbalance associated with ASD. These findings suggest neuroanatomical alterations in cortical regions that underlie the emergence of ASD-related behaviors in this mouse model of the disorder.
ISSN:2076-3425
2076-3425
DOI:10.3390/brainsci13060891