PUBLICATION

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

Authors
Terai, H., Gwedela, M.N.V., Kawakami, K., Aizawa, H.
ID
ZDB-PUB-211104-8
Date
2021
Source
Journal of neurophysiology   126(6): 1934-1942 (Journal)
Registered Authors
Aizawa, Hidenori, Kawakami, Koichi
Keywords
Glutamate, Migraine, Spreading depolarization, Stroke, Zebrafish
MeSH Terms
  • Animals
  • Cerebral Cortex*/drug effects
  • Cerebral Cortex*/physiopathology
  • Cortical Spreading Depression*/drug effects
  • Cortical Spreading Depression*/physiology
  • Disease Models, Animal
  • Excitatory Amino Acid Antagonists/pharmacology*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors*
  • Superior Colliculi*/drug effects
  • Superior Colliculi*/physiology
  • Zebrafish
PubMed
34731067 Full text @ J. Neurophysiol.
Abstract
Spreading depolarization (SD) is a slowly propagating wave of neuronal and glial depolarization. A growing number of studies show that SD and SD-like phenomena play a role in neurological disorders such as migraine, stroke, and traumatic brain injury. Despite the clinical importance of SD, its underlying molecular and cellular mechanisms remain elusive, possibly because of insufficient animal model allowing genetic manipulation. Such a model would also allow high-throughput screening for SD-suppressing drug development. To address this, we developed a novel experimental system to study SD using zebrafish. Electrophysiological recordings in the immobilized adult zebrafish revealed that increasing extracellular potassium concentration elicited SD with a large and long-lasting negative shift of direct current (DC) potential in the optic tectum. It also reduced the oscillatory activity in the extracellular field potential and increased the expression of the immediate early gene c-fos. Pharmacological blocking of the N-methyl-d-aspartate (NMDA) glutamate receptor attenuated the propagation of SD, suggesting that glutamatergic neurotransmission mediated tectal SD in zebrafish. Our analyses revealed that the zebrafish tectum and rodent cortex had similar SD kinetics. The current study provides electrophysiological and pharmacological evidence that zebrafish SD and mammal SD are comparable. This zebrafish SD model is suitable for genetic manipulation and cost-effective high-throughput screening. It could pave the way to novel diagnostic and therapeutic methods applicable to SD-associated neurological disorders.
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