NMDAR dysfunction in autism spectrum disorders: Lessons learned from 10 years of study

Area of Science:

• Neuroscience
• Genetics
• Developmental Disorders

Background:

• Mouse models are crucial for understanding autism spectrum disorders (ASD).
• Numerous molecular, synaptic, neuronal, circuit, and systems-level mechanisms have been proposed for ASD.
• The heterogeneity of ASD necessitates exploring diverse underlying causes.

Purpose of the Study:

• To review the role of NMDA receptor (NMDAR) dysfunction in ASD mouse models.
• To highlight the prevalence and variability of NMDAR abnormalities in ASD.
• To emphasize the need for considering multiple factors in ASD research.

Main Methods:

• Review of existing literature on ASD mouse models.
• Analysis of proposed mechanisms, focusing on NMDAR function.
• Examination of factors influencing NMDAR dysfunction in models.

Main Results:

• NMDAR dysfunction is a frequently observed mechanism in ASD mouse models, with hypofunction being more common.
• Not all ASD mouse models exhibit NMDAR dysfunction, suggesting variability.
• Factors such as genetic background, sex, age, and brain region influence findings.

Conclusions:

• NMDAR dysfunction is a significant, but not universal, mechanism in ASD.
• The heterogeneity of ASD is reflected in varied NMDAR roles across models.
• Comprehensive analysis requires considering multiple variables in ASD mouse studies.