Cited by 38Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionAmino Acid Enzymes and Metabolism

GABA Transporter GAT1: A Crucial Determinant of GABAB Receptor Activation in Cortical Circuits?

Gonzalez-Burgos, Guillermo·2010·Advances in Pharmacology

Abstract

The GABA transporter 1 (GAT1), the main plasma membrane GABA transporter in brain tissue, mediates translocation of GABA from the extracellular to the intracellular space. Whereas GAT1-mediated uptake could generally terminate the synaptic effects of GABA, recent studies suggest a more complex physiological role. This chapter reviews evidence suggesting that in hippocampal and neocortical circuits, GAT1-mediated GABA transport regulates the electrophysiological effects of GABA(B) receptor (GABA(B)R) activation by synaptically-released GABA. Contrasting with synaptic GABA(A) receptors, GABA(B)Rs display high GABA binding affinity, slow G protein-coupled mediated signaling, and a predominantly extrasynaptic localization. Such GABA(B)R properties determine production of slow inhibitory postsynaptic potentials (IPSPs) and slow presynaptic effects. Such effects possibly require diffusion of GABA far away from the release sites, and consequently both GABA(B)R-mediated IPSPs and presynaptic effects are strongly enhanced when GAT1-mediated uptake is blocked. Studies are reviewed here which indicate that GABA(B)R-mediated IPSPs seem to be produced by dendrite-targeting GABA neurons including specifically, although perhaps not exclusively, the neurogliaform cell class. In contrast, the GABA interneuron subtypes that synapse onto the perisomatic membrane of pyramidal cells mostly signal via synaptic GABA(A)Rs. This chapter reviews data suggesting that neurogliaform cells produce electrophysiological effects onto other neurons in the cortical cell network via GABA(B)R-mediated volume transmission that is highly regulated by GAT1 activity. Therefore, the role of GAT1 in controlling GABA(B)R-mediated signaling is markedly different from its regulation of GABA(A)R-mediated fast synaptic transmission.

Integrity signals

Registry

Crossref · 10.1016/s1054-3589(10)58008-6

Cites

129 of 129 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In general, postsynaptic GABABR activation occurs via spillover of GABA from the synapse that in experimental paradigms requires either strong electrical stimulation/trains of stimuli resulting in GABA release from multiple neurons to overcome GABA uptake mechanisms or stimulation under conditions where GABA uptake is pharmacologically blocked.

    “In general, postsynaptic GABABR activation occurs via spillover of GABA from the synapse that in experimental paradigms requires either strong electrical stimulation/trains of stimuli resulting in GABA release from multiple neurons to overcome GABA uptake mechanisms or stimulation under conditions where GABA uptake is pharmacologically blocked (427, 523, 982).”

    From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [427]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Gonzalez-Burgos, G.
Venue
Advances in Pharmacology
Publisher
Elsevier
Published
2010
Volume
58
Pages
175-204
ISSN
1054-3589 (ISSN-L)
OpenAlex
W1585385261
Cited by
38
References
129
Citations by year
2025: 1 · 2021: 1 · 2020: 11 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 1 · 2012: 3
FWCI
3.17
Type
book chapter
Language
en
Open access
closed
Locations
  • Advances in pharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (MH-51234, MH 45156, R01MH051234, P50MH045156)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
GABA transporter 1, GABAB receptors, GABA uptake, volume transmission, neurogliaform cells, presynaptic inhibition, extrasynaptic GABA receptors, GABAA receptor, hippocampus, neocortex, cortical circuits, GABAergic interneurons
MeSH terms
Animals, Cell Membrane, Cerebral Cortex, Humans, Nerve Net, Receptors, GABA-A, Protein Transport, GABA Plasma Membrane Transport Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review