10/03/2026
🎓QBI SEMINAR🎓
Note: Not available via Zoom
Synaptic and Glial Mechanisms of GABA-A Receptor Dysfunction in Epilepsy
Presented by Dr. Nela Durisic
Queensland Brain Institute
University of Queensland
Time: 12-1pm
Date: 11th March
Location: QBI L7 Auditorium
Abstract:
The GABA-A receptor (GABAAR) is a central mediator of both phasic and tonic inhibition in the brain, and pathogenic variants in its subunits are increasingly recognised as important causes of severe paediatric epilepsies. In this seminar, I will present new data examining how distinct receptor variants differentially alter inhibitory signalling, receptor surface expression, and nanoscale organisation at neuronal synapses and in astrocytes.
By dissecting the underlying mechanisms, we distinguish reduced inhibition resulting from impaired receptor trafficking and decreased surface stability from dysfunction caused by altered channel conductance, and relate these molecular mechanisms to clinical severity. Notably, variants that enhance receptor activity can paradoxically be associated with particularly severe phenotypes, and I will present at least one explanation for this. I will also show that profound receptor dysfunction affects excitatory synapse maintenance and that, in cortical astrocytes, epilepsy-associated variants drive context-dependent changes in receptor organisation influenced by neuron–glia interactions.
Together, these findings highlight how altered localisation of GABAARs in neurons and astrocytes destabilises excitation–inhibition balance, leading to inhibitory failure in cortical networks and contributing to diverse epileptic phenotypes. Finally, I will discuss a potential therapeutic avenue leveraging these mechanistic insights that involves drug repurposing.
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