Neuronal Regulation by Luminopsins in Epilepsy Research and Seizure Suppression
Location
Allegheny A, Hotel Madison, JMU
Start Date
4-5-2019 4:40 PM
Description
Over 65 million individuals worldwide suffer from epilepsy, a condition of seizures: abrupt electrical discharges causing muscle spasms, loss of consciousness, and other symptoms. Current epilepsy treatments including seizure-suppressing medications are frequently ineffective or elicit negative side effects. A review of optogenetic neuronal modulation, luciferase optimization, and luminopsin (luminescent opsin) development elucidates the prospect of seizure treatment by luminopsins: chemically-activated luciferases expressed alongside opsins to enable neuronal control without external light hardware. In vitro, the luminopsin LMO3 combining Volvox channelrhodopsin 1 (VChR1) with slow-burn Gaussia luciferase (sbGluc) produced sufficient depolarizing currents to induce action potential firing upon coelenterazine (CTZ) substrate delivery. In rats, inhibitory luminopsin iLMO2 activated during seizure induction significantly decreased seizure on-set time and severity. Employing optogenetic, chemogenic, and bioluminescent mechanisms simultaneously through chemically-activated luminopsins offers the prospect of cell-type, spacial, directional, and temporal neuronal control for epilepsy treatment, without the limitations, ill-effects, or invasivity of previous treatments.
Presentation Type
Presentation
Neuronal Regulation by Luminopsins in Epilepsy Research and Seizure Suppression
Allegheny A, Hotel Madison, JMU
Over 65 million individuals worldwide suffer from epilepsy, a condition of seizures: abrupt electrical discharges causing muscle spasms, loss of consciousness, and other symptoms. Current epilepsy treatments including seizure-suppressing medications are frequently ineffective or elicit negative side effects. A review of optogenetic neuronal modulation, luciferase optimization, and luminopsin (luminescent opsin) development elucidates the prospect of seizure treatment by luminopsins: chemically-activated luciferases expressed alongside opsins to enable neuronal control without external light hardware. In vitro, the luminopsin LMO3 combining Volvox channelrhodopsin 1 (VChR1) with slow-burn Gaussia luciferase (sbGluc) produced sufficient depolarizing currents to induce action potential firing upon coelenterazine (CTZ) substrate delivery. In rats, inhibitory luminopsin iLMO2 activated during seizure induction significantly decreased seizure on-set time and severity. Employing optogenetic, chemogenic, and bioluminescent mechanisms simultaneously through chemically-activated luminopsins offers the prospect of cell-type, spacial, directional, and temporal neuronal control for epilepsy treatment, without the limitations, ill-effects, or invasivity of previous treatments.