Purposes: 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 γ-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.

Pregabalin: Cognitive and behavioural aspects / A. Piazzini, K. Turner, K. El, A. Vignoli, A. Goracci, V. Chiesa, B. La, R. Canger, M. Canevini - In: EPILEPSIA[s.l] : BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND, 2007. - pp. 141-141 (( convegno 27th International Epilepsy Congress tenutosi a Singapore, SINGAPORE nel JUL 08-12, 2007.

Pregabalin: Cognitive and behavioural aspects

A. Vignoli;M. Canevini
2007

Abstract

Purposes: 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 γ-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.
Cortical dysplasia (CD); Metabotropic glutamate receptors; Presynaptic release probability; Short-term plasticity (STP); Whole-cell voltage clamp recording
Settore MED/26 - Neurologia
Settore MED/39 - Neuropsichiatria Infantile
2007
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/201652
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