Purinergic Signalling Mediates Aberrant Excitability of Developing Neuronal Circuits in the Fmr1 Knockout Mouse Model

Authors: Kathryn E. Reynolds, Eileen Huang, Monica Sabbineni, Eliza Wiseman, Nadeem Murtaza, Desmond Ahuja, Matt Napier, Kathryn M. Murphy, Karun K. Singh and Angela L. Scott

Molecular Neurobiology, 23 April 2024

Scientists used using Axion’s hands-free Maestro Pro microelectrode array (MEA) system to evaluate neuron-astrocyte co-cultures in vitro with no labels or dyes.

Neuronal hyperexcitability in cortical circuits is associated with Fragile X syndrome (FXS) and other neurodevelopmental disorders. In this study, researchers examine the effects of astrocytic purinergic signaling on neural connectivity and activity in an FXS disease model, using Axion’s hands-free Maestro Pro microelectrode array (MEA) system to evaluate neuron-astrocyte co-cultures in vitro with no labels or dyes. MEA recordings showed that Fmr1 KO cultures exhibited increased activity and decreased synchrony compared to WT cultures, indicating a hyperexcitable, less organized phenotype. This phenotype was rescued by treatment with P2Y antagonists, suggesting purinergic pathways as a therapeutic target for FXS and potential other neurodevelopmental disorders.