GABAA Receptor-Mediated Tonic Inhibition in Thalamic Neurons

Cope, David W., Hughes, Stuart W. and Crunelli, Vincenzo ORCID: https://orcid.org/0000-0001-7154-9752 2005. GABAA Receptor-Mediated Tonic Inhibition in Thalamic Neurons. Journal of Neuroscience 25 (50) , pp. 11553-11563. 10.1523/JNEUROSCI.3362-05.2005

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Abstract

Tonic GABAA receptor-mediated inhibition is typically generated by subunit-containing extrasynaptic receptors. Because the subunit is highly expressed in the thalamus, we tested whether thalamocortical (TC) neurons of the dorsal lateral geniculate nucleus (dLGN) and ventrobasal complex exhibit tonic inhibition. Focal application of gabazine (GBZ) (50 µM) revealed the presence of a 20 pA tonic current in 75 and 63% of TC neurons from both nuclei, respectively. No tonic current was observed in GABAergic neurons of the nucleus reticularis thalami (NRT). Bath application of 1µM GABA increased tonic current amplitude to 70 pA in 100% of TC neurons, but it was still not observed in NRT neurons. In dLGN TC neurons, the tonic current was sensitive to low concentrations of the subunit-specific receptor agonists allotetrahydrodeoxycorticosterone (100 nM) and 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) (100 nM) but insensitive to the benzodiazepine flurazepam (5 µM). Bath application of low concentrations of GBZ (25–200 nM) preferentially blocked the tonic current, whereas phasic synaptic inhibition was primarily maintained. Under intracellular current-clamp conditions, the preferential block of the tonic current with GBZ led to a small depolarization and increase in input resistance. Using extracellular single-unit recordings, block of the tonic current caused the cessation of low-threshold burst firing and promoted tonic firing. Enhancement of the tonic current by THIP hyperpolarized TC neurons and promoted burst firing. Thus, tonic current in TC neurons generates an inhibitory tone. Its modulation contributes to the shift between different firing modes, promotes the transition between different behavioral states, and predisposes to absence seizures.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	absence epilepsy; -subunit; extrasynaptic receptor; thalamic reticular nucleus; thalamocortical; THIP
Additional Information:	: “Copyright of all material published in The Journal of Neuroscience remains with the authors. The authors grant the Society for Neuroscience an exclusive license to publish their work for the first 6 months. After 6 months the work becomes available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license.(http://creativecommons.org/licenses/) ” See: http://www.jneurosci.org/site/misc/ifa_policies.xhtml
ISSN:	0270-6474
Last Modified:	03 May 2023 23:09
URI:	https://orca.cardiff.ac.uk/id/eprint/1160

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