title: A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures.
abstract: Neural inhibition within the thalamus is integral in shaping thalamocortical oscillatory activity. Fast, synaptic inhibition is primarily mediated by activation of heteropentameric GABA(A) receptor complexes. Here, we examined the synaptic physiology and network properties of mice lacking GABA(A) receptor alpha3, a subunit that in thalamus is uniquely expressed by inhibitory neurons of the reticular nucleus (nRT). Deletion of this subunit produced a powerful compensatory gain in inhibitory postsynaptic response in nRT neurons. Although, other forms of inhibitory and excitatory synaptic transmission in the circuit were unchanged, evoked thalamic oscillations were strongly dampened in alpha3 knockout mice. Furthermore, pharmacologically induced thalamocortical absence seizures displayed a reduction in length and power in alpha3 knockout mice. These studies highlight the role of GABAergic inhibitory strength within nRT in the maintenance of thalamic oscillations, and demonstrate that inhibitory intra-nRT synapses are a critical control point for regulating higher order thalamocortical network activity.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Room M016, Stanford, CA 94305, USA.
authors.forename: Claude M
authors.initials: CM
authors.lastname: Schofield
authors.forename: Max
authors.initials: M
authors.lastname: Kleiman-Weiner
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000818:Animals; D004832:Epilepsy, Absence / Q000503:physiopathology*; D005071:Evoked Potentials / Q000235:genetics; D017353:Gene Deletion; D020646:Intralaminar Thalamic Nuclei / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission; D013788:Thalamus / Q000502:physiology*
chemical_list: C546258:Gabra3 protein, mouse; D011963:Receptors, GABA-A