Evolutionarily conserved wave of neural excitation: spreading depolarization in zebrafish

Upon traumatic brain injury or stroke, damaged neurons and reduced blood supply will excite a limited area of the brain. But this excitation eventually propagates like wave to widen the affected area. This killer-wave like phenomenon is known as spreading depolarization in which neurons and glia exhibit long-lasting depolarization with reduced blood supply. Despite its clinical importance, mechanism underlying it remains unclear.

Since analysis using model animals amenable to the genetic manipulation and pharmacology plays an essential role in addressing the above issue, we set out to establish for the first time zebrafish model of spreading depolarization. Zebrafish, a small tropical fish spawning > 200 eggs per day, is useful due to its high accessibility in genetics, imaging and high-throughput screening of the chemicals. A graduate student, Ms. Terai started this project several years ago and found that physiological and pharmacological characteristics of spreading depolarization were well-conserved between fish and mammals.

Title: Electrophysiological and pharmacological characterization of spreading depolarization in the adult zebrafish tectum

Authors: Haruhi Terai, Mayeso Naomi Victoria Gwedela, Koichi Kawakami, Hidenori Aizawa

Journal: J Neurophysiol (2021) in press [Link]

Results showed that the zebrafish tectum, a layered brain regions integrating the visual information, generated large shift of field potential lasting longer than 60 sec consistent with spreading depolarization in the other species. Interestingly, excitatory transmitter glutamate mediated spreading depolarization in zebrafish as in mammals as well.

We hope to extend this study to identify the compound modulating the susceptibility to the spreading depolarization using zebrafih in near future.