Developmental Disruption of Mef2c in Medial Ganglionic Eminence-Derived Cortical Inhibitory Interneurons Impairs...

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• MEF2C is implicated in neurodevelopmental disorders like autism and schizophrenia.
• MEF2C is essential for excitatory neuron development and synaptic function.
• The role of MEF2C in cortical GABAergic inhibitory neurons is largely unknown.

Purpose of the Study:

• To investigate the function of MEF2C in parvalbumin-expressing interneurons (PV-INs), a key GABAergic cell type.
• To determine the impact of MEF2C loss on PV-IN survival, maturation, and function during development.
• To assess the effects of MEF2C dysfunction on cortical network activity and behavior.

Main Methods:

• Utilized conditional Mef2c gene deletion in mice at embryonic and late postnatal stages.
• Employed slice electrophysiology and in vivo recordings to analyze neuronal activity.
• Conducted behavioral assays to evaluate cognitive, social, and motor functions.

Main Results:

• Embryonic loss of MEF2C in PV-INs reduced their number and impaired molecular/synaptic maturation.
• Early MEF2C deficiency caused abnormal cortical network activity.
• Mice with early MEF2C loss exhibited hyperactivity, stereotypic behaviors, and deficits in cognitive and social behaviors.

Conclusions:

• MEF2C is critical for the proper development and function of cortical GABAergic interneurons, especially PV-INs.
• Embryonic loss of MEF2C leads to GABAergic interneuron dysfunction.
• MEF2C dysfunction in GABAergic INs results in altered brain activity and neurodevelopmental disorder-relevant behaviors.