Document Detail


A gain in GABAA receptor synaptic strength in thalamus reduces oscillatory activity and absence seizures.
MedLine Citation:
PMID:  19380748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Claude M Schofield; Max Kleiman-Weiner; Uwe Rudolph; John R Huguenard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-04-20
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  106     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-06     Completed Date:  2009-05-29     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7630-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Epilepsy, Absence / physiopathology*
Evoked Potentials / genetics
Gene Deletion
Intralaminar Thalamic Nuclei / physiology
Mice
Mice, Knockout
Receptors, GABA-A / genetics,  physiology*
Synapses / physiology*
Synaptic Transmission
Thalamus / physiology*
Grant Support
ID/Acronym/Agency:
NS006477/NS/NINDS NIH HHS; NS007280/NS/NINDS NIH HHS; R01 NS006477/NS/NINDS NIH HHS; R01 NS006477-42/NS/NINDS NIH HHS; R01 NS006477-43/NS/NINDS NIH HHS; R37 NS034774/NS/NINDS NIH HHS; R37 NS034774-12/NS/NINDS NIH HHS; R37 NS034774-13/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Gabra3 protein, mouse; 0/Receptors, GABA-A
Comments/Corrections

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