Linked Life Data

16452257

Source:http://linkedlifedata.com/resource/pubmed/id/16452257

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-4-17
pubmed:abstractText
Functionally, gamma-aminobutyric acid receptor (GABAR)-mediated inhibition can be classified as phasic (synaptic) and tonic (extrasynaptic). The GABARs underlying tonic inhibition assemble from subunits different from those responsible for phasic inhibition. We wanted to assess the excitability of hippocampal pyramidal cell (PC) networks following a selective impairment of tonic inhibition. This is difficult to accomplish by pharmacological means. Because the GABAR alpha5 subunits mostly mediate the tonic inhibition in CA1 and CA3 PCs, we quantified changes in tonic inhibition and examined network excitability in slices of adult gabra5-/- mice. In gabra5-/- CA1 and CA3 PCs tonic inhibitory currents were 60 and 53%, respectively, of those recorded in wild type (WT), with no alterations in phasic inhibition. The amount of tonic inhibition recorded in slices was significantly affected by the method of slice storage (interface or submerged chamber). Field recordings in gabra5-/- CA3 pyramidal layer showed an increased network excitability that was decreased by the GABAR agonist muscimol at a concentration that restored the tonic inhibition of gabra5-/- PCs to the WT level without altering phasic inhibition. Through a battery of pharmacological experiments, we have identified delta subunit-containing GABARs as the mediators of the residual tonic inhibition in gabra5-/- PCs. Our study is consistent with an important role of tonic inhibition in the control of hippocampal network excitability and highlights selective enhancers of tonic inhibition as promising therapeutic approaches for diseases involving network hyperexcitability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2796-807
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16452257-Analysis of Variance, pubmed-meshheading:16452257-Animals, pubmed-meshheading:16452257-Animals, Newborn, pubmed-meshheading:16452257-Bicuculline, pubmed-meshheading:16452257-Dose-Response Relationship, Radiation, pubmed-meshheading:16452257-Drug Interactions, pubmed-meshheading:16452257-Electric Stimulation, pubmed-meshheading:16452257-Evoked Potentials, pubmed-meshheading:16452257-GABA Agonists, pubmed-meshheading:16452257-GABA Antagonists, pubmed-meshheading:16452257-Hippocampus, pubmed-meshheading:16452257-Male, pubmed-meshheading:16452257-Membrane Potentials, pubmed-meshheading:16452257-Mice, pubmed-meshheading:16452257-Mice, Inbred C57BL, pubmed-meshheading:16452257-Mice, Knockout, pubmed-meshheading:16452257-Muscimol, pubmed-meshheading:16452257-Nerve Net, pubmed-meshheading:16452257-Neural Inhibition, pubmed-meshheading:16452257-Nipecotic Acids, pubmed-meshheading:16452257-Oximes, pubmed-meshheading:16452257-Patch-Clamp Techniques, pubmed-meshheading:16452257-Pyramidal Cells, pubmed-meshheading:16452257-Receptors, GABA-A, pubmed-meshheading:16452257-gamma-Aminobutyric Acid
pubmed:year
2006
pubmed:articleTitle
Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABA A receptor alpha5 subunit-deficient mice.
pubmed:affiliation
Interdepartmental PhD Program for Neuroscience and Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural