title: GABA affinity shapes IPSCs in thalamic nuclei.
abstract: 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.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California 94305, USA. cschofie@stanford.edu
authors.forename: Claude M
authors.initials: CM
authors.lastname: Schofield
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D058787:GABA-A Receptor Antagonists; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D013787:Thalamic Nuclei / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid