QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 25, 2007, 27(30):7954-7962; doi:10.1523/JNEUROSCI.0377-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Schofield, C. M. Articles by Huguenard, J. R. Search for Related Content PubMed PubMed Citation Articles by Schofield, C. M. Articles by Huguenard, J. R.

 Previous Article  |  Next Article 

Cellular/Molecular
GABA Affinity Shapes IPSCs in Thalamic Nuclei

Claude M. Schofield and John R. Huguenard

Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305

Correspondence should be addressed to Dr. Claude M. Schofield, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Room M016, Stanford, CA 94305. Email: cschofie{at}stanford.edu

Precise neural inhibition in thalamocortical circuits is required for the generation of sleep spindles and suppression of hypersynchrony associated with epileptiform activity. Accordingly, the time course of GABA_A receptor-mediated IPSC events is an important parameter influencing the strength of inhibitory signaling. In the thalamus, two distinct types of IPSC kinetics are observed: thalamocortical relay neurons in the ventrobasal nucleus (VB) exhibit a fast decaying IPSC, whereas neurons in the adjacent reticular nucleus (RTN) display a long-lasting, slowly decaying IPSC. Here, we used patch-clamp electrophysiology and computational modeling to elucidate the basis for IPSC kinetic heterogeneity in the thalamus. Rapid application of GABA to excised membrane patches revealed that decay kinetics were attributable to intrinsic differences in GABA_A receptor deactivation. Examination of desensitization and gating properties revealed these to be similar in VB and RTN, with the notable lack of fast and long-lasting desensitized states in both cell types. Computational simulations demonstrate that slow GABA binding and unbinding rates could reproduce the characteristic long-lasting IPSCs in RTN cells. These results indicate that within thalamic circuits, a powerful diversity of inhibitory function can result from simple differences in underlying GABA_A receptor affinity.

Key words: kinetics; GABA_A receptor; inhibition; patch clamp; reticular nucleus; thalamus

---

Received Jan. 27, 2007; revised May 25, 2007; accepted June 14, 2007.

Correspondence should be addressed to Dr. Claude M. Schofield, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Room M016, Stanford, CA 94305. Email: cschofie{at}stanford.edu

This article has been cited by other articles:

				C. M. Schofield, M. Kleiman-Weiner, U. Rudolph, and J. R. Huguenard A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures PNAS, May 5, 2009; 106(18): 7630 - 7635. [Abstract] [Full Text] [PDF]

				F. Jia, P. A. Goldstein, and N. L. Harrison The Modulation of Synaptic GABAA Receptors in the Thalamus by Eszopiclone and Zolpidem J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 1000 - 1006. [Abstract] [Full Text] [PDF]

				S. J. Pitt, L. G. Sivilotti, and M. Beato High Intracellular Chloride Slows the Decay of Glycinergic Currents J. Neurosci., November 5, 2008; 28(45): 11454 - 11467. [Abstract] [Full Text] [PDF]

				J. Costa, J. Valls-Sole, F. Valldeoriola, and J. Rumia Subcortical Interactions Between Somatosensory Stimuli of Different Modalities and Their Temporal Profile J Neurophysiol, September 1, 2008; 100(3): 1610 - 1621. [Abstract] [Full Text] [PDF]

				A. Keramidas and N. L. Harrison Agonist-dependent Single Channel Current and Gating in {alpha}4{beta}2{delta} and {alpha}1{beta}2{gamma}2S GABAA Receptors J. Gen. Physiol., January 28, 2008; 131(2): 163 - 181. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help