Authors: Kartik S. Pradeepan, Fraser P. McCready, Wei Wei, Milad Khaki, Wenbo Zhang, Michael W. Salter, James Ellis, and Julio Martinez-Trujillo
Biological Psychiatry Global Open Science, 24 January 2024
The authors use Maestro MEA to perform hands-free electrophysiological experiments in vitro and explore the underlying mechanisms of Rett syndrome.
Rett syndrome (RTT) is a genetic neurodevelopmental disorder characterized by growth, motor, and communication loss typically appearing at 6-18 months in humans. In more than half of RTT cases, patients also experience seizures. Previous research demonstrates that RTT results in neuronal hyperexcitability, yet RTT iPSC-derived neurons exhibit decreased burst frequency in culture. In this study, researchers investigate this paradox, using Axion’s noninvasive Maestro multielectrode array (MEA) platform to evaluate activity and network burst patterns in RTT neurons in vitro in real time.
With Maestro MEA, the team identified a complex burst pattern in the mutant neurons that involves a large initiation burst followed by several high frequency, low amplitude "mini-bursts." The authors call this pattern reverberating super-bursts (RSBs) and warn that it can be misidentified as a single burst if not analyzed with appropriate algorithms, leading to the aforementioned contradiction. Importantly, the researchers also demonstrated that network hyperactivity can be rescued by the calcium chelator EGTA-AM. Overall, these findings provide valuable insights into the underlying mechanisms of RTT and RTT-associated epilepsy and may point to novel pharmacological interventions.
