The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
GABAAreceptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol
Abstract
The neurotransmitter GABA mediates the majority of rapid inhibition in the CNS. Inhibition can occur via the conventional mechanism, the transient activation of subsynaptic GABA A receptors (GABA A-Rs), or via continuous activation of high-affinity receptors by low concentrations of ambient GABA, leading to “tonic” inhibition that can control levels of excitability and network activity. The GABA A-R α4 subunit is expressed at high levels in the dentate gyrus and thalamus and is suspected to contribute to extrasynaptic GABA A-R-mediated tonic inhibition. Mice were engineered to lack the α4 subunit by targeted disruption of the Gabra4 gene. α4 Subunit knockout mice are viable, breed normally, and are superficially indistinguishable from WT mice. In electrophysiological recordings, these mice show a lack of tonic inhibition in dentate granule cells and thalamic relay neurons. Behaviorally, knockout mice are insensitive to the ataxic, sedative, and analgesic effects of the novel hypnotic drug, gaboxadol. These data demonstrate that tonic inhibition in dentate granule cells and thalamic relay neurons is mediated by extrasynaptic GABA A-Rs containing the α4 subunit and that gaboxadol achieves its effects via the activation of this GABA A-R subtype.
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Cites
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Cited by
General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal
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“In mice, it induces sedation largely via α4-containing GABA A receptor”
BackgroundExtrasynaptic GABA A Receptors: Form, Pharmacology, and Function
Belelli, D., Harrison, N. L., Maguire, J., Macdonald, R. L., Walker, M. C., & Cope, D. W. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3340-09.2009 · Cited by 464
“Furthermore, 4 and subunits colocalize with each other and are found predominantly at extrasynaptic sites (Jia et al., 2005), a feature confirmed by the loss of tonic inhibition in TC neurons of 4 subunit knock-out mice (Chandra et al., 2006).”
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Metadata
- Authors
- Chandra, D., Jia, F., Liang, J., Peng, Z., Suryanarayanan, A., Werner, D. F., Spigelman, I., Houser, C. R., Olsen, R. W., Harrison, N. L., & Homanics, G. E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-10-10
- Volume
- 103
- Issue
- 41
- Pages
- 15230-15235
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1968579780
- Cited by
- 314
- References
- 61
- FWCI
- 9.14
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: GABAAreceptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. https://app.cochat.ai/papers/10.1073/pnas.0604304103
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- Chandra, D., Jia, F., Liang, J., Peng, Z., Suryanarayanan, A., Werner, D. F., Spigelman, I., Houser, C. R., Olsen, R. W., Harrison, N. L., & Homanics, G. E. (2006). GABAAreceptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0604304103
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