Journal
GLIA
Volume 70, Issue 1, Pages 196-214Publisher
WILEY
DOI: 10.1002/glia.24106
Keywords
astroglia; brain excitability; calcium imaging; eaat2; epilepsy; glutamate; zebrafish
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Funding
- Forschungskredit der Universitat Zurich [K-74417-01-01]
- RCN FRIPRO Research Grants [314189, 314212]
- Schweizerischer Nationalfonds zur Forderung der Wissenschaftlichen Forschung [31003A_173083]
- Flanders Science Foundation (FWO) Grant
- Samarbeidsorganet Helse Midt-Norge-NTNU [20163]
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The loss of function in the astroglia predominant eaat2a gene in zebrafish leads to altered neuronal and astroglial networks, resulting in epileptic seizures and increased extracellular glutamate levels. Interestingly, while hyperexcitability is observed during seizures, basal neuronal and astroglial activity is reduced, leading to decreased overall locomotion in eaat2a(-/-) mutant animals.
Astroglial excitatory amino acid transporter 2 (EAAT2, GLT-1, and SLC1A2) regulates the duration and extent of neuronal excitation by removing glutamate from the synaptic cleft. Hence, an impairment in EAAT2 function could lead to an imbalanced brain network excitability. Here, we investigated the functional alterations of neuronal and astroglial networks associated with the loss of function in the astroglia predominant eaat2a gene in zebrafish. We observed that eaat2a(-/-) mutant zebrafish larvae display recurrent spontaneous and light-induced seizures in neurons and astroglia, which coincide with an abrupt increase in extracellular glutamate levels. In stark contrast to this hyperexcitability, basal neuronal and astroglial activity was surprisingly reduced in eaat2a(-/-) mutant animals, which manifested in decreased overall locomotion. Our results reveal an essential and mechanistic contribution of EAAT2a in balancing brain excitability, and its direct link to epileptic seizures.
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