Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency.

Hyperfunction of PSD-95 causes neuronal hyperexcitability and cognitive deficits in MEF2C haploinsufficiency, highlighting a potential therapeutic target.

• Why it matters: Understanding the molecular mechanisms behind MEF2C haploinsufficiency syndrome is crucial because current treatments do not address the underlying causes of neurodevelopmental and epileptic symptoms.
• What they did: The study used mouse models with MEF2C haploinsufficiency to examine changes in PSD-95 levels, synaptic structure, and neuronal excitability, employing knockdown and inhibition techniques to test effects.
• The result: Reducing PSD-95 levels or disrupting its interaction with NMDA receptors alleviated hyperexcitability and improved cognitive behaviors, suggesting PSD-95 as a promising target for therapy.