Common circuit defect of excitatory-inhibitory balance in mouse models of autism
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.
- Common circuit defect of excitatory-inhibitory balance in mouse models of autism
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Journal of Neurodevelopmental Disorders
Volume 1, Issue 2 , pp 172-181
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- Springer US
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- Author Affiliations
- 1. Center for Brain Science, Dept. Molecular & Cellular Biology, Harvard University, 52 Oxford St., Cambridge, MA, 02138, USA
- 2. FM Kirby Neurobiology Center, Dept. Neurology, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115, USA
- 3. HHMI, Stanford School of Medicine, 1050 Arastradero Road (B249F), Palo Alto, CA, 94304, USA