Common circuit defect of excitatory-inhibitory balance in mouse models of autism
By Nadine Gogolla, J. LeBlanc, K. Quast, T. Sūdhof, Michela Fagiolini, Takao K. Hensch. Journal of Neurodevelopmental Disorders, 2009
628 citations recorded by the source corpus.
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.
Subfields: Cognitive Neuroscience, Developmental Neuroscience, Genetics
View Paper: https://www.semanticscholar.org/paper/cd4c14dee412209fc3c7d2b08f79d5625ec9330b
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cognitive Neuroscience
- Janet F. Werker
- Y. Dan
- Takao K. Hensch
- Daphne Bavelier
- Dennis M. Levi
- Roger Li
- D. Feldman
- Stephen Grossberg
In Developmental Neuroscience
In Genetics
Citations in the corpus
- Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits (2014, neutral): “…of ASD (Belmonte et al., 2004) proposed to cause failure in differentiating signals from noise, prevent development of normal longrange cortical-cortical and cortical-subcortical communications, and underlie neocortical excitation/inhibition imbalance (Sporns et al., 2000; Gogolla et al., 2009).”
- Removing brakes on adult brain plasticity: from molecular to behavioral interventions (2010, background): “Consistent with the theme developed here (Morishita and Hensch, 2008), one purported mechanism of action of these drugs may be to restore a more normal E/I balance (which is commonly impaired in such disorders) (Rubenstein and Merzenich, 2003; Polleux and Lauder, 2004; Gogolla et al., 2009).”
- Critical periods in speech perception: new directions. (2015, background): “Notably, many mental illnesses that include language impairment—such as schizophrenia and autism—are of neurodevelopmental origin and share defects in the triggers and brakes that normally regulate CP timing (Gogolla et al. 2009, Insel 2010, Rubenstein & Merzenich 2003).”
- Alterations in aperiodic and periodic EEG activity in young children with Down syndrome (2024, unknown): “Indeed, elevated gamma activity has been observed in other neurodevelopmental disorders hypothesized to have altered E/I balance, including Fragile X Syndrome (FXS) and autism (Wilkinson and Nelson, 2021; Rojas and Wilson, 2014; Gabard-Durnam et al., 2019; Gogolla et al., 2009).”
- Alterations in aperiodic and periodic EEG activity in young children with Down syndrome (2024, unknown): “Indeed, elevated gamma activity has been observed in other neurodevelopmental disorders hypothesized to have altered E/I balance, including Fragile X Syndrome (FXS) and autism (Wilkinson and Nelson, 2021; Rojas and Wilson, 2014; Gabard-Durnam et al., 2019; Gogolla et al., 2009).”