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Glia. 2015 Oct;63(10):1784-96. doi: 10.1002/glia.22844. Epub 2015 Apr 27.

Astrocytic glutamate uptake is slow and does not limit neuronal NMDA receptor activation in the neonatal neocortex.

Author information

1
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts.
2
Neuroscience Program, Tufts Sackler School of Biomedical Sciences, Boston, Massachusetts.
3
Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.

Abstract

Glutamate uptake by astrocytes controls the time course of glutamate in the extracellular space and affects neurotransmission, synaptogenesis, and circuit development. Astrocytic glutamate uptake has been shown to undergo post-natal maturation in the hippocampus, but has been largely unexplored in other brain regions. Notably, glutamate uptake has never been examined in the developing neocortex. In these studies, we investigated the development of astrocytic glutamate transport, intrinsic membrane properties, and control of neuronal NMDA receptor activation in the developing neocortex. Using astrocytic and neuronal electrophysiology, immunofluorescence, and Western blot analysis we show that: (1) glutamate uptake in the neonatal neocortex is slow relative to neonatal hippocampus; (2) astrocytes in the neonatal neocortex undergo a significant maturation of intrinsic membrane properties; (3) slow glutamate uptake is accompanied by lower expression of both GLT-1 and GLAST; (4) glutamate uptake is less dependent on GLT-1 in neonatal neocortex than in neonatal hippocampus; and (5) the slow glutamate uptake we report in the neonatal neocortex corresponds to minimal astrocytic control of neuronal NMDA receptor activation. Taken together, our results clearly show fundamental differences between astrocytic maturation in the developing neocortex and hippocampus, and corresponding changes in how astrocytes control glutamate signaling.

KEYWORDS:

EAAT1; EAAT2; GLAST; GLT-1; developmental plasticity; glial development; membrane resistance; postnatal development

PMID:
25914127
PMCID:
PMC4534348
DOI:
10.1002/glia.22844
[Indexed for MEDLINE]
Free PMC Article

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