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Glutamate Uptake by Astrocytic Transporters

  • Konstantin Mergenthaler
  • Franziska Oschmann
  • Klaus ObermeyerEmail author
Chapter
Part of the Springer Series in Computational Neuroscience book series (NEUROSCI)

Abstract

Astrocytes express glutamate transporters at high density at perisynaptic processes which can tightly control extracellular glutamate levels in proximity of postsynaptic receptors with the potential to modulate functional neuronal activity. Glutamate uptake by these transporters also closely depends on activity-dependent extracellular ion concentrations and may also be regulated by the astrocyte’s intracellular calcium. On the other hand, intracellular \(\mathrm{Ca}^{2+}\) dynamics in the astrocyte too can be modulated by glutamate uptake, with potential for functionally relevant interactions with neural activity. Here, we introduce original modeling arguments to study functional implications of glutamate uptake by astrocytes both on their physiology and on that of neurons. In the first case, we consider the contribution of \(\mathrm{{Na^+}}\) and \(\mathrm{{K^+}}\) homeostasis to astrocytic glutamate uptake, revealing that intracellular anisotropy could account for spatial segregation of transporter- versus receptor-mediated calcium signaling pathways. In the second case, we study how regulation of extracellular glutamate levels by astrocytic transporters could affect tuning responses of primary sensory areas, linking our analysis to experimental observations in the ferret’s primary visual cortex by Schummers et al. (2008, Science 320:1638). We conclude that glutamate uptake by astrocytes can modulate function of neuronal circuits in multiple ways that may look subtle at individual synaptic contacts, but at network level, lead instead to functionally relevant changes in neuronal tuning and stimulus discrimination.

Keywords

Sodium-Calcium-Exchanger (NCX) Sodium Network dynamics Dynamic astrocyte-neuron interactions Postynaptic coupling NMDA-receptors 

Abbreviations

AMPA(AMPAR)

\(\upalpha \)-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (receptor)

CICR

\(\mathrm{Ca}^{2+}\)-induced \(\mathrm{Ca}^{2+}\) release

EAAT

excitatory amino acid transporters

EPSC

excitatory postsynaptic current

\(\mathrm{{GABA}}\)

\(\upgamma \)-aminobutyric acid

GABAR

\(\mathrm{{GABA_A}}\) receptor

GLAST

glutamate aspartate transporter

GLT1

type 1 glutamate transporter

HWHM

half width at half maximum

mGluR

metabotropic glutamate receptor

IP\(_3\)R

Inositol 1,4,5-trisphosphate receptor

NCX

Na\(^+\)/Ca\(^{2+}\)exchanger

NKP

Na\(^+\)/K\(^{+}\)ATPase

NMDA (NMDAR)

N-Methyl-d-aspartate (receptor)

TBOA

textscdl-threo-\(\beta \)-benzyloxyaspartate

V1

primary visual cortex

Notes

Acknowledgements

The authors wish to thank Jeremy Petravicz and Mriganka Sur for insightful discussions and Maurizio De Pittà for helping to revise and edit this manuscript in its final form. This work was supported by the Bundesministerium für Bildung und Forschung to KM (grant 01GQ-1009) and by the Deutsche Forschungsgemeinschaft to FO (Graduiertenkolleg 1589).

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Konstantin Mergenthaler
    • 1
  • Franziska Oschmann
    • 1
  • Klaus Obermeyer
    • 1
    Email author
  1. 1.Neural Information Processing, Electrical Engineering & Computer Science and Bernstein Center for Computational NeuroscienceTechnische Universität BerlinBerlinGermany

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