Title
Activity-dependent regulation of astrocyte GAT levels during synaptogenesis
Academic Program
Neuroscience
UMMS Affiliation
Department of Neurobiology; Freeman Lab; Graduate School of Biomedical Sciences, Neuroscience Program
Publication Date
2014-10
Document Type
Article
Disciplines
Developmental Neuroscience | Molecular and Cellular Neuroscience
Abstract
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.
DOI of Published Version
10.1038/nn.3791
Source
Nat Neurosci. 2014 Oct;17(10):1340-50. doi: 10.1038/nn.3791. Epub 2014 Aug 24. Link to article on publisher's site
Journal/Book/Conference Title
Nature neuroscience
Related Resources
PubMed ID
25151265
Repository Citation
Muthukumar A, Stork T, Freeman MR. (2014). Activity-dependent regulation of astrocyte GAT levels during synaptogenesis. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1038/nn.3791. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1873