Glutamate spillover augments GABA synthesis and release from axodendritic synapses in rat hippocampus.

Stafford MM, Brown MN, Mishra P, Stanwood GD, Mathews GC
Hippocampus. 2010 20 (1): 134-44

PMID: 19338018 · PMCID: PMC2810457 · DOI:10.1002/hipo.20600

Tight coupling between gamma-aminobutyric acid (GABA) synthesis and vesicle filling suggests that the presynaptic supply of precursor glutamate could dynamically regulate inhibitory synapses. Although the neuronal glutamate transporter excitatory amino acid transporter 3 (EAAT3) has been proposed to mediate such a metabolic role, highly efficient astrocytic uptake of synaptically released glutamate normally maintains low-extracellular glutamate levels. We examined whether axodendritic inhibitory synapses in stratum radiatum of hippocampal area CA1, which are closely positioned among excitatory glutamatergic synapses, are regulated by synaptic glutamate release via presynaptic uptake. Under conditions of spatially and temporally coordinated release of glutamate and GABA within pyramidal cell dendrites, blocking glial glutamate uptake enhanced quantal release of GABA in a transporter-dependent manner. These physiological findings correlated with immunohistochemical studies revealing expression of EAAT3 by interneurons and uptake of D-asparate into putative axodendritic inhibitory terminals only when glial uptake was blocked. These results indicate that spillover of glutamate between adjacent excitatory and inhibitory synapses can occur under conditions when glial uptake incompletely clears synaptically released glutamate. Our anatomical studies also suggest that perisomatic inhibitory synapses, unlike synapses within dendritic layers of hippocampus, are not capable of glutamate uptake and therefore transporter-mediated dynamic regulation of inhibition is a unique feature of axodendritic synapses that may play a role in maintaining a homeostatic balance of inhibition and excitation.

Copyright 2009 Wiley-Liss, Inc.

MeSH Terms (19)

Animals Axons CA1 Region, Hippocampal D-Aspartic Acid Dendrites Excitatory Amino Acid Transporter 3 gamma-Aminobutyric Acid Glutamic Acid Interneurons In Vitro Techniques Neural Inhibition Neuroglia Neurons Presynaptic Terminals Pyramidal Cells Rats Rats, Sprague-Dawley Synapses Synaptic Transmission

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