Distribution of extracellular glutamate in the neuropil of hippocampus

Melissa A. Herman, Ben Nahir, Craig Jahr

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Reported values of extracellular glutamate concentrations in the resting state depend on the method of measurement and vary ~1000-fold. As glutamate levels in the micromolar range can cause receptor desensitization and excitotoxicity, and thus affect neuronal excitability, an accurate determination of ambient glutamate is important. Part of the variability of previous measurements may have resulted from the sampling of glutamate in different extracellular compartments, e.g., synaptic versus extrasynaptic volumes. A steep concentration gradient of glutamate between these two compartments could be maintained, for example, by high densities of glutamate transporters arrayed at the edges of synapses. We have used two photon laser scanning microscopy and electrophysiology to investigate whether extracellular glutamate is compartmentalized in acute hippocampal slices. Pharmacological blockade of NMDARs had no effect on Ca2+ transients generated in dendritic shafts or spines of CA1 pyramidal neurons by depolarization, suggesting that ambient glutamate is too low to activate a significant number of NMDARs. Furthermore, blockade of transporters did not flood the synapse with glutamate, indicating that synaptic NMDARs are not protected from high concentrations of extrasynaptic glutamate. We suggest that, in the CA1 region of hippocampus, glutamate transporters do not create a privileged space within the synapse but rather keep ambient glutamate at very low levels throughout the neuropil.

Original languageEnglish (US)
Article numbere26501
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 1 2011

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Neuropil
hippocampus
glutamates
Glutamic Acid
Hippocampus
Synapses
Amino Acid Transport System X-AG
synapse
transporters
Electrophysiology
Pyramidal Cells
Depolarization
electrophysiology
Photons
Confocal Microscopy
Neurons
Microscopic examination
Spine
lasers
Pharmacology

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Distribution of extracellular glutamate in the neuropil of hippocampus. / Herman, Melissa A.; Nahir, Ben; Jahr, Craig.

In: PLoS One, Vol. 6, No. 11, e26501, 01.11.2011.

Research output: Contribution to journalArticle

Herman, Melissa A. ; Nahir, Ben ; Jahr, Craig. / Distribution of extracellular glutamate in the neuropil of hippocampus. In: PLoS One. 2011 ; Vol. 6, No. 11.
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