Authors: Assunta Merolla, Caterina Michetti, Matteo Moschetta, Francesca Vacca, Lorenzo Ciano, Laura Emionite, Simonetta Astigiano, Alessandra Romei, Simone Horenkamp, Ken Berglund, Robert E. Gross, Fabrizia Cesca, Elisabetta Colombo and Fabio Benfenati
Nature Communications, 04 July 2024
Scientists studying optogenetics describe a potential therapeutic strategy for treating drug-resistant epilepsies, using hands-free Maestro MEA to record functional neural activity in vitro.
Nearly a third of people with epilepsy are resistant to antiepileptic drugs, prompting the need for alternative therapeutic strategies. Optogenetics has emerged as a potential strategy, but reliably illuminating deep brain regions is challenging. In this study, researchers developed a pH-sensitive inhibitory luminopsin (pHIL) composed of a luciferase-based light generator, fluorescent pH sensor, and an optogenetic actuator. When neurons undergo hyperactivity, the intracellular pH drops, ultimately activating halorhodopsin and reducing the hyperexcitability in just the hyperactive neurons. The authors used Axion’s noninvasive Maestro MEA to record neural activity coinciding with reduced pH in vitro, first validating E2GFP as a sufficient intracellular pH sensor, then assessing the capacity of pHIL to inhibit activity in primary hippocampal neurons. Together with other findings, the “results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug refractory epilepsy.”
