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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1998-8-25
|
| pubmed:abstractText |
Neuronal migration disorders (NMD) are involved in a variety of different developmental disturbances and in therapy-resistant epilepsy. The cellular mechanisms underlying the pronounced hyperexcitability in dysplastic cortex are not well understood and demand further clinical and experimental analyses. We used a focal freeze-lesion model in cerebral cortex of newborn rats to study the functional consequences of NMD. Intracellular recordings from supragranular regular spiking cells in cortical slices from adult sham-operated rats revealed normal passive and active intrinsic membrane properties and normal stimulus-evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively). Regular spiking neurons recorded in rat dysplastic cortex showed on average a significantly smaller action potential amplitude, a slower spike rise, and a less steep primary frequency-current relationship. Stimulus-elicited EPSPs in NMD-affected cortex consisted of multiphasic burst discharges, which coincided with extracellular field potentials and lasted 150-800 ms. These epileptiform responses could be recorded at membrane potentials between -50 and -110 mV and were blocked by -2-amino-5-phosphonovaleric acid (APV), indicating the involvement of N-methyl--aspartate (NMDA) receptors. Isolated NMDA-mediated and APV-sensitive EPSPs could be recorded at membrane potentials negative to -70 mV, suggesting that NMDA receptors are activated at relatively negative membrane potentials. In comparison with the controls, polysynaptic IPSPs mediated by the gamma-aminobutyric acid (GABA) type A and B receptor were either absent or reduced in peak conductance in microgyric cortex by 27% (P < 0.05) and 17%, respectively. However, monosynaptic IPSPs recorded in the presence of ionotropic glutamate receptor antagonists revealed a similar efficacy in NMD and control cortex, indicating that GABAergic neurons in microgyric cortex get a weaker excitatory input. Our data indicate that the expression of epileptiform activity in NMD-affected cortex rather results from an imbalance between excitatory and inhibitory synaptic transmission than from alterations in the intrinsic membrane properties. This imbalance is caused by an increase in NMDA-receptor-mediated excitation in pyramidal neurons and a concurrent decrease of glutamatergic input onto inhibitory interneurons.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2,3-dioxo-6-nitro-7-sulfamoylbenzo(f...,
http://linkedlifedata.com/resource/pubmed/chemical/2-Amino-5-phosphonovalerate,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0022-3077
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
80
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
92-102
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9658031-2-Amino-5-phosphonovalerate,
pubmed-meshheading:9658031-Aging,
pubmed-meshheading:9658031-Animals,
pubmed-meshheading:9658031-Animals, Newborn,
pubmed-meshheading:9658031-Brain Diseases,
pubmed-meshheading:9658031-Cell Movement,
pubmed-meshheading:9658031-Evoked Potentials,
pubmed-meshheading:9658031-Excitatory Amino Acid Antagonists,
pubmed-meshheading:9658031-Excitatory Postsynaptic Potentials,
pubmed-meshheading:9658031-Interneurons,
pubmed-meshheading:9658031-Membrane Potentials,
pubmed-meshheading:9658031-Neocortex,
pubmed-meshheading:9658031-Neurons,
pubmed-meshheading:9658031-Pyramidal Cells,
pubmed-meshheading:9658031-Quinoxalines,
pubmed-meshheading:9658031-Rats,
pubmed-meshheading:9658031-Rats, Wistar,
pubmed-meshheading:9658031-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:9658031-Synapses,
pubmed-meshheading:9658031-Synaptic Transmission
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Characterization of neuronal migration disorders in neocortical structures. II. Intracellular in vitro recordings.
|
| pubmed:affiliation |
Institute of Neurophysiology, University of Düsseldorf, D-40001 Dusseldorf, Germany.
|
| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
|