Impaired developmental switch of short-term plasticity in pyramidal cells of dysplastic cortex.
OBJECTIVE
Human cortical dysplasia (CD) has a strong clinical association with intractable epilepsy. It is believed that neuronal networks of CD are hyperexcitable, which may initiate seizures. The underlying mechanisms are, however, still poorly understood. We have studied the alterations of synaptic properties in a rat model of CD, in utero irradiation.


METHODS
Pregnant rats on E17 were exposed to 225 cGy of external gamma-irradiation and offspring were used for experiments. Coronal somatosensory brain slices were obtained from 13 - 60-day-old rats. Visualized whole-cell recordings were performed on pyramidal neurons in layer V of control neocortex and the middle region of dysplastic cortex. Short-term plasticity (STP) of evoked excitatory postsynaptic currents (EPSCs) was induced by 5-pulse (20 Hz or 50 Hz) train stimulations.


RESULTS
STP of EPSCs in pyramidal cells of the normal cortex induced by 5-pulse train stimulation (20 Hz or 50 Hz) switched from depression at P13-15 to facilitation at P28-35 and P55-60. However, STP in CD at P28-35 and P 55-60 still showed depression. The failure rate of synaptic responses to the first pulse of the stimulation tested at P 28-35 was significantly lower in CD than in controls. The depression of STP in CD at P28-35 was altered neither by blocking the desensitization of glutamate receptors nor by blocking postsynaptic Ca(2+) rise. It was also not affected by an antagonist of mGluR2/3, LY341495.


CONCLUSIONS
Our results indicate that, compared to control cortex, the presynaptic release probability of excitatory synapses in CD pyramidal cells at P28-35 and P55-60 remains abnormally high and reduced tonic activity of presynaptic mGluR2/3 may contribute to this elevated release probability.
Chen
Huan-Xin
HX
Department of Neurological Surgery, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA. chenhx@neurosurgery.ufl.edu
Xiang
Hui
H
Roper
Steven N
SN
D000016:Abnormalities, Radiation-Induced / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2