Sashmita of Northwestern University Feinberg School of Medicine, Chicago, USA

Sodium channel, are linked to monogenic causes of variable onset epilepsy, autism spectrum disorder, and epileptic encephalopathies. While the mechanism for SCN2A haploinsufficiency and concomitant loss of function has been explored in detail, the impact of missense SCN2A variants is less clear due to a paucity of studies looking at neuronal function. To address this roadblock, we applied high-throughput all-optical electrophysiology to patient-derived neurons with the p.M1879T variant compared to CRIPSR-corrected isogenic lines. We complemented the findings in these ‘Optopatch’ experiments with conventional patch-clamp electrophysiology. The p.M1879T variant neurons had significantly increased firing rates compared to isogenic controls at higher and longer optical stimuli, indicating increased firing reserve. These neurons tended to fire later into the pulse as well, demonstrating resistance to depolarization block. Machine learning-based classification was able to differentiate the neuron genotype with high accuracy (>95%) based on these evoked firing parameters. We further applied high-throughput optical electrophysiology to characterize the effect of different clinically available sodium channel blocking agents on evoked neuronal firing: carbamazepine, phenytoin, lacosamide, and cenobamate. Compared to DMSO-treated controls, all anti-seizure medications resulted in a dose-dependent reduction of evoked firing. Select concentrations of drugs were able to partially rescue the variant firing close to isogenic levels, demonstrating translational application of our in vitro findings. These results provide the first application of high-throughput iPSC-derived neuron electrophysiology and pharmacology in SCN2A-related disorders, demonstrating proof that this platform can be readily applied to a variety of monogenic models of epilepsy

Biography:

Sashmita Panda received the B.Tech degree in Electronics and Telecommunication Engi- neering from Sanjaya Memorial Institute of Technology (SMIT), Odisha, India, in 2009, and the M.Tech degree in Electrical Engineering from the National Institute of Technology (NIT), Rourkela, India, in 2015. She received her Ph.D. degree from the G. S. Sanyal School of Telecommunications, IIT Kharagpur, India, in 2023. From 2009 to 2013, she worked as an Assistant Professor at two different Engineering Institutes, Odisha. From 2015 to 2016, she was an Assistant Professor at KL University, Vijayawada, Andhra Pradesh. She has 5 years of teaching experience. After her Ph.D. thesis submission, from 2022 to 2023, she worked as a Research Associate at IIT Indore, India. Since April 2023, she is working as a Postdoctoral Fellow in the Department of Neurology at Northwestern University Feinberg School of Medicine, Chicago, USA. Her research interests include computational neuroscience, performing cell culturing on stem cells and HEK cells. Differentiating the neurons from the induced pluripotent stem cells (iPSCs) by neural induction, and patch-clamp recordings on neurons. She is focused on combining computational neuroscience with ‘wet lab’ neuroscience techniques. She has enhanced her skillset by rapidly learning iPSC culture and differentiation into neurons, as well as patch clamp recordings and analyzing neuronal population datasets on MEA and Optopatch using machine learning techniques to allow for unbiased approaches. With a broad background and specialized training and expertise in computational data analysis, she has investigated various study disciplines. Her research interest are diverse and include computational neuroscience, machine learning modeling on ALS, sleep and circadian behavior in humans and Drosophila, machine learning (ML) applications, biological neural communication,computational neuroscience, Spiking Neural Networks, communication theory, and innovative wireless communication systems. At present she has 10 published journals, two are under review, one is under submission and 21 conference publications and 3 book chapters.

Email:

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