BEGIN:VCALENDAR VERSION:2.0 PRODID:IEEE vTools.Events//EN CALSCALE:GREGORIAN BEGIN:VTIMEZONE TZID:America/New_York BEGIN:DAYLIGHT DTSTART:20260308T030000 TZOFFSETFROM:-0500 TZOFFSETTO:-0400 RRULE:FREQ=YEARLY;BYDAY=2SU;BYMONTH=3 TZNAME:EDT END:DAYLIGHT BEGIN:STANDARD DTSTART:20261101T010000 TZOFFSETFROM:-0400 TZOFFSETTO:-0500 RRULE:FREQ=YEARLY;BYDAY=1SU;BYMONTH=11 TZNAME:EST END:STANDARD END:VTIMEZONE BEGIN:VEVENT DTSTAMP:20260804T041726Z UID:F16854A1-D57F-4ECF-B6D2-64ED0374F2A3 DTSTART;TZID=America/New_York:20260925T100000 DTEND;TZID=America/New_York:20260925T110000 DESCRIPTION:Abstract:\n\nSodium channel\, are linked to monogenic causes of variable onset epilepsy\, autism spectrum disorder\, and epileptic enceph alopathies. While the mechanism for SCN2A haploinsufficiency and concomita nt loss of function has been explored in detail\, the impact of missense S CN2A variants is less clear due to a paucity of studies looking at neurona l function. To address this roadblock\, we applied high-throughput all-opt ical electrophysiology to patient-derived neurons with the p.M1879T varian t compared to CRIPSR-corrected isogenic lines. We complemented the finding s in these ‘Optopatch’ experiments with conventional patch-clamp elect rophysiology. The p.M1879T variant neurons had significantly increased fir ing rates compared to isogenic controls at higher and longer optical stimu li\, indicating increased firing reserve. These neurons tended to fire lat er into the pulse as well\, demonstrating resistance to depolarization blo ck. Machine learning-based classification was able to differentiate the ne uron genotype with high accuracy (>95%) based on these evoked firing param eters. We further applied high-throughput optical electrophysiology to cha racterize the effect of different clinically available sodium channel bloc king agents on evoked neuronal firing: carbamazepine\, phenytoin\, lacosam ide\, and cenobamate. Compared to DMSO-treated controls\, all anti-seizure medications resulted in a dose-dependent reduction of evoked firing. Sele ct concentrations of drugs were able to partially rescue the variant firin g close to isogenic levels\, demonstrating translational application of ou r in vitro findings. These results provide the first application of high-t hroughput 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\n\nSpeaker(s): Sashmi ta\, \n\nAgenda: \n10.00 am - Introduction of the speaker\n\n10.05 am - Pr esentation\n\n10.45 am - Q&A session\n\n11.00 am - Conclusion\n\nVirtual: https://events.vtools.ieee.org/m/570819 LOCATION:Virtual: https://events.vtools.ieee.org/m/570819 ORGANIZER:mguduri@ltu.edu SEQUENCE:18 SUMMARY:xcitatory Neuron Dysfunction and Pharmacologic Rescue in an SCN2A G ain-of-Function Variant Associated with Early-Onset Epilepsy using Machine Learning approach URL;VALUE=URI:https://events.vtools.ieee.org/m/570819 X-ALT-DESC:Description: <br /><p>Abstract:</p>\n<p>Sodium channel\, are lin ked to monogenic causes of variable onset epilepsy\, autism spectrum disor der\, and epileptic encephalopathies. While the mechanism for SCN2A haploi nsufficiency 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 appli ed high-throughput all-optical electrophysiology to patient-derived neuron s with the p.M1879T variant compared to CRIPSR-corrected isogenic lines. W e complemented the findings in these &lsquo\;Optopatch&rsquo\; experiments with conventional patch-clamp electrophysiology. The p.M1879T variant neu rons had significantly increased firing rates compared to isogenic control s at higher and longer optical stimuli\, indicating increased firing reser ve. These neurons tended to fire later into the pulse as well\, demonstrat ing resistance to depolarization block. Machine learning-based classificat ion was able to differentiate the neuron genotype with high accuracy (&gt\ ;95%) based on these evoked firing parameters. We further applied high-thr oughput optical electrophysiology to characterize the effect of different clinically available sodium channel blocking agents on evoked neuronal fir ing: carbamazepine\, phenytoin\, lacosamide\, and cenobamate. Compared to DMSO-treated controls\, all anti-seizure medications resulted in a dose-de pendent reduction of evoked firing. Select concentrations of drugs were ab le to partially rescue the variant firing close to isogenic levels\, demon strating translational application of our in vitro findings. These results provide the first application of high-throughput iPSC-derived neuron elec trophysiology and pharmacology in SCN2A-related disorders\, demonstrating proof that this platform can be readily applied to a variety of monogenic models of epilepsy</p><br /><br />Agenda: <br /><p>10.00 am - Introduction of the speaker</p>\n<p>10.05 am - Presentation</p>\n<p>10.45 am - Q&amp\; A session</p>\n<p>11.00 am - Conclusion</p> END:VEVENT END:VCALENDAR