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Fishing for developmental mechanisms driving stress-responsive behaviour and epilepsy

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In vertebrates, the nervous system is among the first organ systems to develop, but the process of neuronal differentiation is long-drawn and regulated by numerous factors. In my talk, I will discuss how major defects in this process lead to neurological diseases, while subtle differences in development result in the establishment of individual behaviours.  

I will first detail how we used a combination of behavioural and molecular biology tools to understand the mechanisms underlying epilepsy, a common neurodevelopmental disorder. Specifically, we found a new role for an mTOR inhibitory factor, depdc5, in the formation of inhibitory neurons. Defective mTOR regulation and GABAergic neuron maturation independently lead to epilepsy when DEPDC5 is mutated.  

In the second half of my talk, I will discuss my work on the ontogeny of stress resilience. Individuals in a population respond differently to stressful situations, with some being more resilient than others. However, it remains challenging to determine the developmental window when resilience is established as a trait using mammalian embryos. Using a high-throughput behavioural assay that I recently developed, we established that stress resilience is observed early in life as a stable and heritable trait. Using a combination of pharmacological and genetic tools, we found that this trait is regulated positively by neuropeptides and negatively by the innate immune complement system.  


About Speaker: 

Amrutha Swaminathan is currently a postdoctoral fellow with Prof Gil Levkowitz at the Weizmann Institute of Science, Israel. She works on the developmental origins of stress resilience using zebra fish as a model. She tries to understand the developmental basis for neurological disorders such as epilepsy, and also how small developmental differences can determine individual behaviour.



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