Journal article
Which GABAA Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus?
The Journal of neuroscience, Vol.28(6), pp.1421-1426
02/06/2008
DOI: 10.1523/JNEUROSCI.4751-07.2008
PMID: 18256262
Abstract
GABA
A
receptors (GABA
A
Rs) assembled of different subunits mediate tonic and phasic inhibition in hippocampal neurons. CA1/CA3 pyramidal cells (PCs) predominantly express α5 subunits whereas dentate gyrus granule cells (DGGCs) and molecular layer (ML) interneurons predominantly express δ subunits. Both α5- and δ-containing GABA
A
Rs mediate tonic inhibition. We have shown previously that mice lacking α5 subunits (
Gabra5
−/−
) have a residual tonic current in CA1/CA3 PCs because of an upregulation of δ subunits, but the basis of the residual tonic current in DGGCs and ML interneurons of mice lacking the δ subunit (
Gabrd
−/−
) is still unknown. We now show that wild-type DGGCs have a small tonic current mediated by α5 subunit-containing GABA
A
Rs responsible for ∼29% of the total tonic current. To better identify the GABA
A
Rs mediating tonic inhibition in hippocampal neurons, we generated mice lacking both α5 and δ subunits (
Gabra5/Gabrd
−/−
). Recordings from CA1/CA3 PCs, DGGCs, and ML interneurons in these mice show an absence of tonic currents without compensatory changes in spontaneous IPSCs (sIPSCs), sEPSCs, and membrane resistance. The absence of tonic inhibition results in spontaneous gamma oscillations recordable
in vitro
in the CA3 pyramidal layer of these mice, which can be mimicked in wild-type mice by blocking α5 subunit-containing GABA
A
Rs with 50 n
m
L-655,708. In conclusion, depending on the cell type, the α5 and δ subunits are the principal GABA
A
R subunits responsible for mediating the lion's share of tonic inhibition in hippocampal neurons.
Details
- Title: Subtitle
- Which GABAA Receptor Subunits Are Necessary for Tonic Inhibition in the Hippocampus?
- Creators
- Joseph Glykys - Interdepartmental PhD Program for Neuroscience andEdward O Mann - Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, California 90095Istvan Mody - Interdepartmental PhD Program for Neuroscience and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.28(6), pp.1421-1426
- DOI
- 10.1523/JNEUROSCI.4751-07.2008
- PMID
- 18256262
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- Society for Neuroscience
- Language
- English
- Date published
- 02/06/2008
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984020637902771
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