title: 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.
  
  
  BACKGROUND
  The online version of this article (doi:10.1007/s11689-009-9023-x) contains supplementary material, which is available to authorized users.
authors.forename: Nadine
authors.initials: N
authors.lastname: Gogolla
authors.forename: Jocelyn J
authors.initials: JJ
authors.lastname: Leblanc
authors.forename: Kathleen B
authors.initials: KB
authors.lastname: Quast
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
authors.forename: Michela
authors.initials: M
authors.lastname: Fagiolini
authors.forename: Takao K
authors.initials: TK
authors.lastname: Hensch