Investigation of Cotrical Microcircuit Dysfunction in a Mouse Model of Dravet Syndrome

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Faculty

Assistant Professor

Project Summary

This summer, I had the privilege of working in the lab of Dr. Ethan Goldberg at CHOP through PURM. The Goldberg lab’s main interest is in pediatric epilepsies and most members of the lab study Dravet syndrome, a neurodevelopmental disorder that is defined by temperature-sensitive seizures that progress to treatment-resistant epilepsy and intellectual disability with features of autism spectrum disorder. Although we know the underlying genetic cause of Dravet syndrome, the exact mechanism through which the mutations cause seizures and other Dravet syndrome symptoms is still unknown. Recent studies by the lab and others have discovered dysfunction in three major classes of interneurons in Dravet syndrome and my project this summer has been trying to uncover circuit level defects that arise as a result of this known interneuron dysfunction.

The focus of my summer has been to investigate a disinhibitory circuit in the cerebral cortex composed of vasoactive intestinal peptide interneurons (VIP-INs) and somatostatin interneurons (SST-INs), both of which are dysfunctional in Dravet syndrome. VIP-INs strongly inhibit SST-INs which in turn inhibit pyramidal neurons, the main excitatory neurons in the cerebral cortex. Using pharmacological and optogenetic activation of VIP-INs, my summer project attempts to determine whether this disynaptic inhibition is impaired in Dravet syndrome.

Through this investigation, I learned how to do whole-cell recordings, one of the fundamental techniques used in the field of modern neuroscience. It was especially interesting to integrate it together with other lab techniques that I had already learned because it allowed me to have a better understanding and control over the whole scientific process of the project. I also gained experience in MATLAB programming to perform data analysis and create figures as well as some basic experience with two-photon imaging.

The most exciting part of my research experience this summer was getting to apply the material I learned in the classroom towards making real world discoveries in the lab. It has really reinforced my interest in pursuing research, especially in neuroscience. Seeing the enthusiasm and dedication of other lab members has inspired and excited me to continue working in the lab during the school year, where I hope to continue making progress towards a stronger conclusion on the projects that started this summer.