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Autism spectrum disorders (ASDs) arise from altered development of the central nervous system, and manifest behaviorally as social interaction deficits and restricted and repetitive behaviors. Alterations to parvalbumin (PV) expressing interneurons have been implicated in the neuropathological and behavioral deficits in autism. In addition, perineuronal nets (PNNs), specialized extracellular matrix structures that enwrap the PV-expressing neurons, also may be altered, which compromises neuronal function and susceptibility to oxidative stress. In particular, the prefrontal cortex (PFC), which regulates several core autistic traits, relies on the normal organization of PNNs and PV-expressing cells, as well as other neural circuit elements. Consequently, we investigated whether PNNs and PV-expressing cells were altered in the PFC of the CNTNAP2 knockout mouse model of ASD and whether these contributed to core autistic-like behaviors in this model system. We observed an overexpression of PNNs, PV-expressing cells, and PNNs enwrapping PV-expressing cells in adult CNTNAP2 mice. Transient digestion of PNNs from the prefrontal cortex (PFC) by injection of chondroitinase ABC in CNTNAP2 mutant mice rescued some of the social interaction deficits, but not the restricted and repetitive behaviors. These findings suggest that the neurobiological regulation of PNNs and PVs in the PFC contribute to social interaction behaviors in neurological disorders including autism.
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Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders
Autism spectrum disorder (ASD) is comprised of several conditions characterized by alterations in social interaction, communication, and repetitive behaviors. Genetic and environmental factors contribute to the heterogeneous development of ASD behaviors. Several rodent models display ASD-like phenotypes, including repetitive behaviors. In this review article, we discuss the potential neural mechanisms involved in repetitive behaviors in rodent models of ASD and related neuropsychiatric disorders. We review signaling pathways, neural circuits, and anatomical alterations in rodent models that display robust stereotypic behaviors. Understanding the mechanisms and circuit alterations underlying repetitive behaviors in rodent models of ASD will inform translational research and provide useful insight into therapeutic strategies for the treatment of repetitive behaviors in ASD and other neuropsychiatric disorders.
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- Award ID(s):
- 1652432
- PAR ID:
- 10249165
- Date Published:
- Journal Name:
- Frontiers in Cellular Neuroscience
- Volume:
- 14
- ISSN:
- 1662-5102
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fncel.2020.592710
