HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 586/4/965    most recent jphysiol.2007.145375v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Peden, D. R. Articles by Lambert, J. J. PubMed PubMed Citation Articles by Peden, D. R. Articles by Lambert, J. J. Related Collections Neuroscience

¹ Neurosciences Institute, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
² Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH – 8057 Zurich, Switzerland
³ Merck Research Laboratories, Merck & Co, 126 E. Lincoln Ave, Rahway, NJ 07065, USA
⁴ Department of Anaesthesiology, University of Pittsburgh, Pittsburgh, PA, USA

Thalamic ventrobasal (VB) relay neurones express multiple GABA_A receptor subtypes mediating phasic and tonic inhibition. During postnatal development, marked changes in subunit expression occur, presumably reflecting changes in functional properties of neuronal networks. The aims of this study were to characterize the properties of synaptic and extrasynaptic GABA_A receptors of developing VB neurones and investigate the role of the ₁ subunit during maturation of GABA-ergic transmission, using electrophysiology and immunohistochemistry in wild type (WT) and ₁^0/0 mice and mice engineered to express diazepam-insensitive receptors (_1H101R, _2H101R). In immature brain, rapid (P8/9–P10/11) developmental change to mIPSC kinetics and increased expression of extrasynaptic receptors (P8–27) formed by the ₄ and subunit occurred independently of the ₁ subunit. Subsequently ( P15), synaptic ₂ subunit/gephyrin clusters of WT VB neurones were replaced by those containing the ₁ subunit. Surprisingly, in ₁^0/0 VB neurones the frequency of mIPSCs decreased between P12 and P27, because the ₂ subunit also disappeared from these cells. The loss of synaptic GABA_A receptors led to a delayed disruption of gephyrin clusters. Despite these alterations, GABA-ergic terminals were preserved, perhaps maintaining tonic inhibition. These results demonstrate that maturation of synaptic and extrasynaptic GABA_A receptors in VB follows a developmental programme independent of the ₁ subunit. Changes to synaptic GABA_A receptor function and the increased expression of extrasynaptic GABA_A receptors represent two distinct mechanisms for fine-tuning GABA-ergic control of thalamic relay neurone activity during development.

(Received 23 September 2007; accepted after revision 30 November 2007; first published online 6 December 2007)
Corresponding author J. J. Lambert: Neurosciences Institute, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. Email: j.j.lambert{at}dundee.ac.uk

This article has been cited by other articles:

				M. B. Herd, A. R. Haythornthwaite, T. W. Rosahl, K. A. Wafford, G. E. Homanics, J. J. Lambert, and D. Belelli The expression of GABAA {beta} subunit isoforms in synaptic and extrasynaptic receptor populations of mouse dentate gyrus granule cells J. Physiol., February 15, 2008; 586(4): 989 - 1004. [Abstract] [Full Text] [PDF]