Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-10-11
pubmed:abstractText
GABA(A) receptors generate both phasic and tonic forms of inhibition. In hippocampal pyramidal neurons, GABA(A) receptors that contain the alpha5 subunit generate a tonic inhibitory conductance. The physiological role of this tonic inhibition is uncertain, although alpha5GABA(A) receptors are known to influence hippocampal-dependent learning and memory processes. Here we provide evidence that alpha5GABA(A) receptors regulate the strength of the depolarizing stimulus that is required to generate an action potential in pyramidal neurons. Neurons from alpha5 knock-out (alpha5-/-) and wild-type (WT) mice were studied in brain slices and cell cultures using whole cell and perforated-patch-clamp techniques. Membrane resistance was 1.6-fold greater in alpha5-/- than in WT neurons, but the resting membrane potential and chloride equilibrium potential were similar. Membrane hyperpolarization evoked by an application of exogenous GABA was greater in WT neurons. Inhibiting the function of alpha5GABA(A) receptor with nonselective (picrotoxin) or alpha5 subunit-selective (L-655,708) compounds depolarized WT neurons by approximately 3 mV, whereas no change was detected in alpha5-/- neurons. The depolarizing current required to generate an action potential was twofold greater in WT than in alpha5-/- neurons, whereas the slope of the input-output relationship for action potential firing was similar. We conclude that shunting inhibition mediated by alpha5GABA(A) receptors regulates the firing of action potentials and may synchronize network activity that underlies hippocampal-dependent behavior.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2244-54
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17715197-Action Potentials, pubmed-meshheading:17715197-Animals, pubmed-meshheading:17715197-Cells, Cultured, pubmed-meshheading:17715197-Electrophysiology, pubmed-meshheading:17715197-Excitatory Amino Acid Agonists, pubmed-meshheading:17715197-Excitatory Amino Acid Antagonists, pubmed-meshheading:17715197-Excitatory Postsynaptic Potentials, pubmed-meshheading:17715197-GABA Antagonists, pubmed-meshheading:17715197-GABA-A Receptor Antagonists, pubmed-meshheading:17715197-Hippocampus, pubmed-meshheading:17715197-Imidazoles, pubmed-meshheading:17715197-Membrane Potentials, pubmed-meshheading:17715197-Mice, pubmed-meshheading:17715197-Mice, Inbred C57BL, pubmed-meshheading:17715197-Mice, Knockout, pubmed-meshheading:17715197-Patch-Clamp Techniques, pubmed-meshheading:17715197-Picrotoxin, pubmed-meshheading:17715197-Pyramidal Cells, pubmed-meshheading:17715197-Receptors, GABA-A, pubmed-meshheading:17715197-gamma-Aminobutyric Acid
pubmed:year
2007
pubmed:articleTitle
Alpha5GABAA receptors regulate the intrinsic excitability of mouse hippocampal pyramidal neurons.
pubmed:affiliation
Department of Physiology, University of Toronto, Toronto, ON, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't