Watch Dr Alexander Bryson accept the research grant award and hear a bit about the project.
Project Summary:
Epilepsy is a common disorder in which episodes of abnormal electrical activity (seizures) arise within the brain. The first-line treatment of epilepsy is with antiseizure medications, yet many patients experience persistent seizures that are refractory to existing drugs.
Although the molecular targets of many antiseizure medications have been identified, it remains unknown how these drugs modify brain activity to prevent seizures, which limits efforts to develop more effective therapies. One reason for this knowledge gap is a lack of tools at our disposal to probe brain activity at sufficient detail to untangle how antiseizure medications work.
This project will tackle this issue using a technique to image brain activity at very fine-grained detail, known as two-photon calcium imaging, and a model of the brain grown in a dish, known as a brain organoid. This approach will enable us to characterise how antiseizure medications modulate brain activity, and may unlock the potential to develop new treatments that are tailored for specific forms of epilepsy.
Outcomes:
Dr Bryson and his team aimed to use optical imaging and brain organoids to understand how antiseizure medications (ASMs) modify the properties of neuronal networks to prevent seizures. They hypothesised that “treated” organoids would exhibit measurable changes in network properties compared to “untreated” organoids, and that these findings may provide novel biomarkers for ASM drug discovery and enhance the search for newer and more effective treatments.
After imaging around 30 brain organoids, they observed marked variability in their activity: many organoids had under 10 active cells, and several organoids exhibited non-physiological activity such as global synchrony. As a result, they had to change their experimental method. Instead of using brain organoids, they will use in-vivo 2-photon imaging in animal models to characterise the impact of ASMs on neuronal network properties.
The findings from their work with brain organoids still have important implications for the field, as it reveals the need for standardised methods when recording activity in brain organoids. Dr Bryson’s team outlined a detailed methodology for calcium imaging and MEA recordings, which was published in the Journal of Neuroscience Methods.
Outcomes submitted January 2024.
Publications:
Oliva M, Bourke J, Kornienko D, et al. Standardizing a method for functional assessment of neural networks in brain organoids. Journal of Neuroscience Methods. 2024;409:110178. doi:10.1016/j.jneumeth.2024.110178
The Brain Foundation is dedicated to funding the next generation of Australian research into brain disorders, diseases, and injuries, with the ultimate goal of advancing diagnoses, treatments, and patient outcomes.