How do Anti-Epileptic Drugs Work?

Project Lead

Dr Chris French

frenchc@unimelb.edu.au

+61 3 8344 3276

Project Details

Despite many years of use and research, it is still not clear how even some of the oldest forms of antiepileptic drugs (AED’s) work. What is known is generally based on the effects of these compounds on single neurons, rather than examining how activity of the whole inter-connected neural network of the mammalian CNS is modulated. This project involves studying the effects of AED’s at several levels of organization of the CNS – single channel (voltage-gated sodium, potassium and calcium channels), single neuron, principal neuron/interneuron dynamics, as well as glial cell effects.

Patch clamp techniques are used for recording dissociated neuron and neurons in the intact brain slice, and these observations will be extended with high-speed calcium imaging with conventional microscopy as well as multiphoton techniques. This projects affords excellent opportunities for skill development in electrophysiology, pharmacology advanced microscopy and computational neuroscience as well as conference presentation and publication opportunities.

Researchers

Dr Chris French

Professor David Williams

Professor Terry O’Brien

Research Outcomes

• Taing, K. D., O’Brien, T. J., Williams, D. A., & French, C. R. (2017). Anti-Epileptic Drug Combination Efficacy in an In Vitro Seizure Model – Phenytoin and Valproate, Lamotrigine and Valproate. PLOS One, 12(1), e0169974

• Zeng, Z., Hill-Yardin, E. L., Williams, D. A., O’Brien, T. J., Serelis, A., & French, C. R. (2016). The Effect of Phenytoin on Sodium Conductances in Rat Hippocampal CA1 Pyramidal Neurons. Journal of Neurophysiology, J Neurophysiol. 2016 Oct 1;116(4):1924-1936

• Boiteux, C., Vorobyov, I., French, R. J., French, C., Yarov-yarovoy, V., Allen, T(2014). Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel. PNAS, 111(36), 13057–13062.