Reduced inhibition in an animal model of cortical dysplasia.
Cortical dysplasia has a strong association with epilepsy in humans, but the underlying mechanisms for this are poorly understood. In utero irradiation of rats produces diffuse cortical dysplasia and neuronal heterotopia in the neocortex and hippocampus. Using in vitro neocortical slices, whole-cell patch-clamp recordings were obtained from pyramidal neurons in dysplastic cortex and control neocortex. Spontaneous IPSCs were reduced in amplitude (35%) and frequency (70%) in pyramidal cells from dysplastic cortex. Miniature IPSCs were reduced in frequency (66%) in dysplastic cortex. Two additional measures of cortical inhibition, monosynaptic evoked IPSCs and paired pulse depression of evoked EPSCs, were also impaired in dysplastic cortex. Spontaneous EPSCs were increased in amplitude (42%) and frequency (77%) in dysplastic cortex, but miniature EPSCs were not different between the two groups. These data demonstrate significant physiological impairment in inhibitory synaptic transmission in experimental cortical dysplasia. This supports previous immunohistochemical findings in this model and observations in humans of a reduction in the density of inhibitory interneurons in dysplastic cortex.
Zhu
W J
WJ
Department of Neurological Surgery, University of Florida, and Malcolm Randall Veterans Administration Medical Center, Gainesville, Florida 32610-0265, USA.
Roper
S N
SN
D000016:Abnormalities, Radiation-Induced / Q000503:physiopathology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002828:Choristoma / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000528:radiation effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D058787:GABA-A Receptor Antagonists; D005720:Gamma Rays; D066298:In Vitro Techniques; D018811:Maternal Exposure; D019579:Neocortex / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects; D009433:Neural Inhibition / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D017966:Pyramidal Cells / Q000378:metabolism / Q000503:physiopathology* / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000528:radiation effects; D013779:Tetrodotoxin / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D013779:Tetrodotoxin