Title

Activity-dependent regulation of astrocyte GAT levels during synaptogenesis

Student Author(s)

Allie Muthukumar

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

Link to Article in PubMed

PubMed ID

25151265

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