From synapses to circuits: What mouse models have taught us about how autism spectrum disorder impacts hippocampal function

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that impacts a variety of cognitive and behavioral domains. While a genetic component of ASD has been well-established, none of the numerous syndromic genes identified in humans accounts for more than 1% of the clinical patients...

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Published in:Neuroscience and biobehavioral reviews 2024-03, Vol.158, p.105559-105559, Article 105559
Main Authors: Severino, Leandra, Kim, Jinhyun, Nam, Min-Ho, McHugh, Thomas J.
Format: Article
Language:English
Subjects:
Animal models
Autism spectrum disorder
E/I balance
Glia
Hippocampus
In vivo physiology
Neural circuits
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Summary:Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that impacts a variety of cognitive and behavioral domains. While a genetic component of ASD has been well-established, none of the numerous syndromic genes identified in humans accounts for more than 1% of the clinical patients. Due to this large number of target genes, numerous mouse models of the disorder have been generated. However, the focus on distinct brain circuits, behavioral phenotypes and diverse experimental approaches has made it difficult to synthesize the overwhelming number of model animal studies into concrete throughlines that connect the data across levels of investigation. Here we chose to focus on one circuit, the hippocampus, and one hypothesis, a shift in excitatory/inhibitory balance, to examine, from the level of the tripartite synapse up to the level of in vivo circuit activity, the key commonalities across disparate models that can illustrate a path towards a better mechanistic understanding of ASD’s impact on hippocampal circuit function. •Alterations in hippocampal activity and function are consistently found across ASD patients and model animals.•Abnormal connectivity and excitatory/inhibitory imbalances in the hippocampus are commonly observed in ASD model animals.•Morphological and transcriptional changes in hippocampal astrocytes and microglia play a crucial role in ASD pathology.•Dysregulation of hippocampal oscillations and network coordination is observed in diverse ASD model animals.
ISSN:0149-7634
1873-7528
DOI:10.1016/j.neubiorev.2024.105559