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Different transmitter transients underlie presynaptic cell type specificity of GABA A,slow and GABA A,fast
Open accessAbstract
Phasic (synaptic) and tonic (extrasynaptic) inhibition represent the two most fundamental forms of GABA(A) receptor-mediated transmission. Inhibitory postsynaptic currents (IPSCs) generated by GABA(A) receptors are typically extremely rapid synaptic events that do not last beyond a few milliseconds. Although unusually slow GABA(A) IPSCs, lasting for tens of milliseconds, have been observed in recordings of spontaneous events, their origin and mechanisms are not known. We show that neocortical GABA(A,slow) IPSCs originate from a specialized interneuron called neurogliaform cells. Compared with classical GABA(A,fast) IPSCs evoked by basket cells, single spikes in neurogliaform cells evoke extraordinarily prolonged GABA(A) responses that display tight regulation by transporters, low peak GABA concentration, unusual benzodiazepine modulation, and spillover. These results reveal a form of GABA(A) receptor mediated communication by a dedicated cell type that produces slow ionotropic responses with properties intermediate between phasic and tonic inhibition.
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“These features combined with the dense local ramification of NGFC axons are considered to underlie the ability of NGFCs to mediate volume transmission leading to slow dual component (GABAAR- and GABABR-mediated) inhibition at virtually any postsynaptic element within their dense axonal plexus (550, 926, 927, 1074, 1086).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1074]
In the citing paper
“While neocortical NGFCs can be found throughout all layers, they are particularly enriched in supragranular layers and form a major constituent cell population in L1 (564, 858, 1017, 1074, 1086, 1134).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1074]
In the citing paper
“Of particular interest, in contrast to the rapid and synchronous IPSCs produced by PVBCs, transmission from NGFCs generates long-lasting IPSCs resulting from prolonged GABA transients (550, 1074, 1086) that arise from the unusual synaptic architecture where bouton density is high but close apposition to specialized postsynaptic densities is low (550, 751, 858, 1074) (FIGURE 13C).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1074]
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“Electrophysiological recordings from pairs of NGFCs demonstrate a marked functional connectivity with each other (48, 550, 926, 1074).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1074]
In the citing paper
“These remarkably slow kinetics are not fully attributable to dendritic filtering, asynchronous release, spillover, nor the properties of the GABAARs themselves (however, see Refs. 483, 1264) but are primarily due to the spatiotemporal profile of GABA release from this interneuron subtype (see sect. IVL) (167, 550, 870, 1074).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [1074]
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Self-citation
Metadata
- Authors
- Szabadics, J., Tamás, G., & Soltesz, I.
- Affiliations
- University of California, Irvine (US)
- University of Szeged (HU)
- *Department of Anatomy and Neurobiology, University of California, 193 Irvine Hall, Irvine, CA 92697; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-09-11
- Volume
- 104
- Issue
- 37
- Pages
- 14831-14836
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1964542
- OpenAlex
- W2004000308
- Cited by
- 170
- References
- 49
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 9 · 2020: 8 · 2019: 3 · 2018: 9 · 2017: 6 · 2016: 7 · 2015: 6 · 2014: 14 · 2013: 9 · 2012: 8
- FWCI
- 7.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institute of Neurological Disorders and Stroke (R29NS035915, R01NS035915, NS-35915, R37NS035915)
- 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 › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- GABAA receptor, tonic inhibition, extrasynaptic inhibition, phasic inhibition, neurogliaform cells, basket cells, inhibitory postsynaptic currents, benzodiazepine modulation, GABA transporters, neocortex, interneurons, presynaptic neurotransmitter release
- MeSH terms
- Zolpidem, Action Potentials, Animals, Interneurons, Kainic Acid, Kinetics, Models, Neurological, Neural Inhibition, Pyridines, Receptors, GABA-A, Synapses, N-Methylaspartate, Rats, Wistar, Presynaptic Terminals, Patch-Clamp Techniques, GABA Agonists, Neocortex, Rats
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