Common circuit defect of excitatory-inhibitory balance in mouse models of autism

Abstract

One unifying explanation for the complexity of Autism Spectrum Disorders (ASD) may lie in the disruption of excitatory/inhibitory (E/I) circuit balance during critical periods of development. We examined whether Parvalbumin (PV)-positive inhibitory neurons, which normally drive experience-dependent circuit refinement (Hensch Nat Rev Neurosci 6:877–888, 1), are disrupted across heterogeneous ASD mouse models. We performed a meta-analysis of PV expression in previously published ASD mouse models and analyzed two additional models, reflecting an embryonic chemical insult (prenatal valproate, VPA) or single-gene mutation identified in human patients (Neuroligin-3, NL-3 R451C). PV-cells were reduced in the neocortex across multiple ASD mouse models. In striking contrast to controls, both VPA and NL-3 mouse models exhibited an asymmetric PV-cell reduction across hemispheres in parietal and occipital cortices (but not the underlying area CA1). ASD mouse models may share a PV-circuit disruption, providing new insight into circuit development and potential prevention by treatment of autism.

Cited by papers we hold 19

• Exposure to GABAA Receptor Antagonist Picrotoxin in Pregnant Mice Causes Autism-Like Behaviors and Aberrant Gene Expression in Offspring · 2022
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• GABAergic System Dysfunction in Autism Spectrum Disorders · 2022
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• mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity · 2021
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• Longitudinal EEG power in the first postnatal year differentiates autism outcomes · 2019
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• Alterations in Gut Glutamate Metabolism Associated with Changes in Gut Microbiota Composition in Children with Autism Spectrum Disorder · 2019
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• Phase-amplitude coupling and epileptogenesis in an animal model of mesial temporal lobe epilepsy · 2018
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• Reduced auditory cortical adaptation in autism spectrum disorder · 2018
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• Disinhibition, an emerging pharmacology of learning and memory [version 1; referees: 3 approved] · 2017
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• Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism · 2017
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• Reduction in parvalbumin expression not loss of the parvalbumin-expressing GABA interneuron subpopulation in genetic parvalbumin and shank mouse models of autism · 2016
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• Shank3-mutant mice lacking exon 9 show altered excitation/inhibition balance, enhanced rearing, and spatial memory deficit · 2015
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• Prefrontal Cortex and Social Cognition in Mouse and Man · 2015
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• GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders · 2014
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• Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses · 2013
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• Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI. · 2012
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• Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders · 2012
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• Alterations of GABAergic Signaling in Autism Spectrum Disorders · 2011
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• Autism: A “Critical Period” Disorder? · 2011
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• mGluR5-Antagonist Mediated Reversal of Elevated Stereotyped, Repetitive Behaviors in the VPA Model of Autism · 2011
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