GABA Spillover Activates Postsynaptic GABAB Receptors to Control Rhythmic Hippocampal Activity

Scanziani, Massimo

doi:10.1016/s0896-6273(00)81069-7

Cited by 385Neuroscience and Neuropharmacology ResearchNeural dynamics and brain functionEpilepsy research and treatment

GABA Spillover Activates Postsynaptic GABAB Receptors to Control Rhythmic Hippocampal Activity

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Scanziani, Massimo·2000·Neuron

DOI 10.1016/s0896-6273(00)81069-7

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Abstract

In the hippocampus, interneurons provide synaptic inhibition via the transmitter GABA, which can activate GABA(A) and GABA(B) receptors (GABA(A)Rs and GABA(B)Rs). Generally, however, GABA released by a single interneuron activates only GABA(A)Rs on its targets, despite the abundance of GABA(B)RS. Here, I show that during hippocampal rhythmic activity, simultaneous release of GABA from several interneurons activates postsynaptic GABA(B)Rs and that block of GABA(B)Rs increases oscillation frequency. Furthermore, if GABA uptake is inhibited, even GABA released by a single interneuron is enough to activate GABA(B)Rs. This occurs also on cells not directly contacted by that interneuron, indicating that GABA has to overcome uptake and exit the synaptic cleft to reach GABA(B)RS. Thus, activation of extrasynaptic GABA(B)Rs by pooling of GABA is an important mechanism regulating hippocampal network activity.

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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 [982]

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Authors: Scanziani, M.
Affiliations: University of Zurich (CH)
Corresponding author: Scanziani, Massimo
ORCID: Scanziani, Massimo
Venue: Neuron
Publisher: Elsevier BV
Published: 2000-03
Volume: 25
Issue: 3
Pages: 673-681
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/s0896-6273(00)81069-7
OpenAlex: W2004937932
Cited by: 385
References: 50
Citations by year: 2026: 5 · 2025: 14 · 2024: 10 · 2023: 7 · 2022: 8 · 2021: 11 · 2020: 21 · 2019: 6 · 2018: 6 · 2017: 22 · 2016: 10 · 2015: 16 · 2014: 15 · 2013: 14 · 2012: 16
FWCI: 5.85
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4886 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
Keywords: GABAB receptors, hippocampal interneurons, hippocampal oscillations, GABA uptake, synaptic inhibition, GABAA receptor, oscillation frequency
MeSH terms: Animals, Electric Stimulation, gamma-Aminobutyric Acid, Hippocampus, Interneurons, Membrane Potentials, Neural Inhibition, Periodicity, Pyramidal Cells, Receptors, GABA-B, Rats, In Vitro Techniques

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GABA Spillover Activates Postsynaptic GABAB Receptors to Control Rhythmic Hippocampal Activity

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