Mecp2 deficiency impairs microscale cortical network topology and dynamics in a Rett syndrome mouse model

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Rett syndrome is a neurodevelopmental disorder linked to MECP2 mutations, causing cognitive impairments.
• Mecp2 deficiency in mice disrupts microscale cortical circuits, but cellular-scale network alterations remain unclear.

Purpose of the Study:

• To investigate the impact of Mecp2 deficiency on the development of functional connectivity, network topology, and dynamics in primary cortical cultures.
• To understand how cellular-scale information processing is altered in Mecp2-deficient microscale functional networks.

Main Methods:

• Utilized microelectrode array (MEA) recordings of primary cortical cultures from Mecp2-deficient and wild-type mice.
• Analyzed functional connectivity, network topology, and network dynamics during development.

Main Results:

• Mecp2-deficient cortical networks exhibited slower development and decreased functional connectivity compared to wild-type.
• Network size, density, and connectivity strength were reduced in Mecp2-deficient cultures.
• Altered network topology in Mecp2-deficient circuits indicated decreased efficiency and information-sharing capacity.

Conclusions:

• Mecp2 deficiency leads to developmental deficits in microscale functional networks, potentially underlying cortical decline in Rett syndrome.
• Findings suggest circuit-level targets for therapeutic interventions aimed at restoring microscale network function.
• This study provides an in-vitro model for evaluating therapeutic products for Rett syndrome.