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GABAA autoreceptors enhance GABA release from human neocortex: towards a mechanism for high-frequency stimulation (HFS) in brain?

  • Michela Mantovani
  • Andreas Moser
  • Carola A. Haas
  • Josef Zentner
  • Thomas J. FeuersteinEmail author
Original Article

Abstract

High-frequency stimulation (HFS) in human neocortical slices induces γ-aminobutyric acid (GABA) release via GABAA receptor (GABAAR) activation. The mechanism of this effect and the localization of these GABAARs were now studied. Fresh human neocortical slices were subjected to HFS (130 Hz) in the presence of veratridine (3 µM). As measured by high-performance liquid chromatography, only GABA but not glutamate outflow was affected by HFS/veratridine stimulation. The evoked GABA overflow was abolished by tetrodotoxin and furosemide, suggesting an involvement of action potentials and plasmalemmal chloride gradients. Double immunolabeling showed that GABAARs are localized on soma and dendrites of GABAergic neurons in the human neocortex. Moreover, in support of a terminal localization of GABAARs, the K+-evoked [3H]-GABA release from synaptosomes was enhanced by the GABAAR agonist muscimol (antagonized by GABAAR blockers). We conclude that HFS in human brain neocortex leads to a specific increase of GABA release, which is mediated by facilitatory GABAA autoreceptors located on soma, dendrites, and axon terminals of GABAergic neurons.

Keywords

High-frequency stimulation Potassium depolarization γ-aminobutyric acid (GABA) release GABAA autoreceptor localization Human neocortex slices Human neocortex synaptosomes 

Abbreviations

aCSF

artificial cerebrospinal fluid

AOAA

aminooxyacetic acid

CCC

cation-chloride cotransporter

DAPI

4′,6-diamidine-2-phenylindole dihydrochloride

DL-TBOA

DL-threo-β-benzyloxyaspartic acid

GABA

γ-aminobutyric acid

GABAARs

GABAA receptors

GAD

glutamic acid decarboxylase

GAT

GABA transporter

Glu

glutamate

HFS

high-frequency stimulation

NNC-711

1-diphenylmethyleneaminooxyethyl-l,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride

NPA

(±) nipecotic acid

PB

phosphate buffer

PFA

paraformaldehyde

Ver

veratridine

TTX

tetrodotoxin

Notes

Acknowledgements

M. M. gratefully acknowledges the support by the German Academic Exchange Service (DAAD).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Michela Mantovani
    • 1
  • Andreas Moser
    • 2
  • Carola A. Haas
    • 3
  • Josef Zentner
    • 4
  • Thomas J. Feuerstein
    • 1
    Email author
  1. 1.Section of Clinical Neuropharmacology, Department of NeurosurgeryUniversity Hospital FreiburgFreiburgGermany
  2. 2.Neurochemical Research Group, Department of NeurologyUniversity of LübeckLübeckGermany
  3. 3.Experimental Epilepsy Group, Department of NeurosurgeryUniversity Hospital FreiburgFreiburgGermany
  4. 4.Department of NeurosurgeryUniversity Hospital FreiburgFreiburgGermany

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