PUBLICATION

Loss of glutamate transporter eaat2a leads to aberrant neuronal excitability, recurrent epileptic seizures, and basal hypoactivity

Authors
Hotz, A.L., Jamali, A., Rieser, N.N., Niklaus, S., Aydin, E., Myren-Svelstad, S., Lalla, L., Jurisch-Yaksi, N., Yaksi, E., Neuhauss, S.C.F.
ID
ZDB-PUB-211101-7
Date
2021
Source
Glia   70(1): 196-214 (Journal)
Registered Authors
Hotz, Adriana, Jurisch-Yaksi, Nathalie, Neuhauss, Stephan
Keywords
astroglia, brain excitability, calcium imaging, eaat2, epilepsy, glutamate, zebrafish
MeSH Terms
  • Excitatory Amino Acid Transporter 2/genetics
  • Excitatory Amino Acid Transporter 2/metabolism
  • Glutamic Acid/metabolism
  • Epilepsy*/metabolism
  • Neurons/metabolism
  • Animals
  • Astrocytes/metabolism
  • Seizures/genetics
  • Seizures/metabolism
  • Zebrafish*/metabolism
(all 10)
PubMed
34716961 Full text @ Glia
Abstract
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.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cu3313TgTransgenic Insertion
    jf4TgTransgenic Insertion
      nkUAShspzGCaMP6s13aTgTransgenic Insertion
        nw7TgTransgenic Insertion
          w2
            Point Mutation
            zf498TgTransgenic Insertion
              zh7
                Small Deletion
                1 - 7 of 7
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                Human Disease / Model
                1 - 1 of 1
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                Sequence Targeting Reagents
                Target Reagent Reagent Type
                slc1a2bCRISPR1-slc1a2bCRISPR
                1 - 1 of 1
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                Fish
                Antibodies
                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                cpEGFPEFGcpEGFP
                GAL4EFGGAL4
                GCaMPEFGGCaMP
                1 - 3 of 3
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                Mapping
                No data available