Authors: Hunter Morrill, Ryley Parrish
Mentors: Ryley Parrish
Insitution: Brigham Young University
Spreading depolarizations (SDs) are slow propagating waves of depolarization that move through the brain and have been associated with a wide variety of neuropathologies including the termination of seizures, the cellular correlate of aura in migraines, traumatic brain injury, and ischemic stroke. Though first characterized by Aristides Leão in the 1940s, only a very limited understanding of the mechanisms of SD induction has been achieved. SDs have been induced in mouse models using a variety of techniques, however regardless of the method of induction, high extracellular potassium and/or a strong cellular depolarization have been largely hypothesized as necessary conditions for SD induction. Interestingly, we have recently demonstrated that using a light-induced chloride pump (Halorhodopsin) to drive chloride ions into the neurons can reliably induce SDs even in the absence of high extracellular potassium levels (Parrish, 2023). It was also demonstrated that the triggering of archaerhodopsin, which removes protons from the cell and therefore hyperpolarizes the neuronal membrane without affecting chloride levels, did not induce SDs, suggesting the implication of chloride loading as a primary mechanism in SD induction. This challenges the prevalent hypothesis regarding the induction of SDs and results in a novel method of induction that allows for more characterization of the mechanisms involved. The use of genetically expressed light-gated ion channels or pumps is referred to as optogenetics. Using zebrafish, a common model for electrophysiology recordings that is also cost-effective to genetically manipulate, we have established an optogenetically induced model of SD induction. We are currently characterizing mechanisms that result in optogenetically induced SDs with pharmacology to further our understanding of SD initiation and propagation.
Parrish, R. R.-G.-T. (2023). Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization. The Journal of neuroscience: the official journal of the Society for Neuroscience, 43(5), 685-692.