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Activity-dependent regulation of astrocyte GAT levels during synaptogenesis
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Activity-dependent regulation of astrocyte GAT levels during synaptogenesis
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Journal Article
Activity-dependent regulation of astrocyte GAT levels during synaptogenesis
2014
Overview
Uptake of the neurotransmitter GABA by transporters called GATs is known to influence neuronal GABAergic tone. Here Muthukumar
et al
. show that the wave of synaptogenesis in
Drosophila
brains occurs during the second half of pupal development in an astrocyte-dependent manner. The study also shows that the upregulation of GAT during this process requires astrocytic metabotropic GABA receptors, and this pathway mediates mechanosensory-induced seizure activity in GABAergic mutants with hyperexcitable neurons.
Astrocytic uptake of GABA through GABA transporters (GATs) is an important mechanism regulating excitatory/inhibitory balance in the nervous system; however, mechanisms by which astrocytes regulate GAT levels are undefined. We found that at mid-pupal stages the
Drosophila melanogaster
CNS neuropil was devoid of astrocyte membranes and synapses. Astrocyte membranes subsequently infiltrated the neuropil coordinately with synaptogenesis, and astrocyte ablation reduced synapse numbers by half, indicating that
Drosophila
astrocytes are pro-synaptogenic. Shortly after synapses formed in earnest, GAT was upregulated in astrocytes. Ablation or silencing of GABAergic neurons or disruption of metabotropic GABA receptor 1 and 2 (GABA
B
R1/2) signaling in astrocytes led to a decrease in astrocytic GAT. Notably, developmental depletion of astrocytic GABA
B
R1/2 signaling suppressed mechanosensory-induced seizure activity in mutants with hyperexcitable neurons. These data reveal that astrocytes actively modulate GAT expression via metabotropic GABA receptor signaling and highlight the importance of precise regulation of astrocytic GAT in modulation of seizure activity.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 14/1
/ 14/19
/ 14/28
/ 82
/ Ablation
/ Animal Genetics and Genomics
/ Animals
/ Animals, Genetically Modified
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ GABA
/ GABAergic Neurons - physiology
/ Insects
/ Luminescent Proteins - genetics
/ Luminescent Proteins - metabolism
/ Microscopy, Electron, Transmission
/ Neurons
/ Polymers
