Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-12
pubmed:abstractText
The cortical migration process depends on a number of trophic factors and on the activation of different voltage- and ligand-gated channels. We investigated the role of gamma-aminobutyric acid (GABA) type A receptors in the neuronal migration process of the newborn rat parietal cortex in vivo and in vitro. Local in vivo application of the GABA-A antagonist bicuculline methiodide (BMI) or the agonist muscimol via cortical surface Elvax implants induced prominent alterations in the cortical architecture when compared with untreated or sham-operated controls. BMI- and muscimol-treated animals revealed heterotopic cell clusters in the upper layers and a complete loss of the cortical lamination in the region underlying the Elvax implant. Immunocytochemical staining for glial fibrillary acidic protein, N-methyl-D-aspartate receptors, and GABA demonstrated that heterotopia was not provoked by glial proliferation and confirmed the presence of both glutamatergic and GABAergic neurons. In organotypic neocortical slices from embryonic day 18-19 embryos, application of BMI and to a lesser extent also muscimol induced an increase in the migration speed and an accumulation of neurons in the upper cortical layers. Spontaneous intracellular calcium ([Ca2+]i) oscillations in neocortical slices from newborn rats were abolished by BMI (5 and 20 microM) and muscimol (1 and 10 microM), indicating that both compounds interfere with [Ca2+]i signaling required for normal neuronal migration. Electrophysiological recordings from migrating neurons in newborn rat neocortical slices indicate that long-term application of muscimol causes a pronounced reduction (1 microM muscimol) or blockade (10 microM) in the responsiveness of postsynaptic GABA-A receptors due to a pronounced receptor desensitization. Our results indicate that modulation of GABA-A receptors by compounds acting as agonists or antagonists may profoundly influence the neuronal migration process in the developing cerebral cortex.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1047-3211
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
138-48
pubmed:meshHeading
pubmed-meshheading:16452638-Animals, pubmed-meshheading:16452638-Animals, Newborn, pubmed-meshheading:16452638-Antimetabolites, pubmed-meshheading:16452638-Bicuculline, pubmed-meshheading:16452638-Bromodeoxyuridine, pubmed-meshheading:16452638-Calcium, pubmed-meshheading:16452638-Cell Movement, pubmed-meshheading:16452638-Drug Implants, pubmed-meshheading:16452638-Electrophysiology, pubmed-meshheading:16452638-GABA Agonists, pubmed-meshheading:16452638-GABA Antagonists, pubmed-meshheading:16452638-Glial Fibrillary Acidic Protein, pubmed-meshheading:16452638-Immunohistochemistry, pubmed-meshheading:16452638-Kinetics, pubmed-meshheading:16452638-Muscimol, pubmed-meshheading:16452638-Neocortex, pubmed-meshheading:16452638-Neurons, pubmed-meshheading:16452638-Patch-Clamp Techniques, pubmed-meshheading:16452638-Rats, pubmed-meshheading:16452638-Rats, Wistar, pubmed-meshheading:16452638-Receptors, GABA-A, pubmed-meshheading:16452638-Receptors, N-Methyl-D-Aspartate
pubmed:year
2007
pubmed:articleTitle
GABA-A receptors regulate neocortical neuronal migration in vitro and in vivo.
pubmed:affiliation
Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't