4. In vitro epileptiform activity: role of excitatory amino acids

Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices

“…In a series of studies, Bragin et al (1999Bragin et al ( , 2000Bragin et al ( , 2003 have shown that in vivo oscillatory activity Ͼ200 Hz is spatially restricted to the epileptogenic focus and formulated a hypothesis that the emergence of a hyper-synchronous neuronal sub-network drives seizures (Bragin et al 2002). Pathological HFOs are not only spatially restricted to the site of ictogenesis, but they are also enhanced immediately at the seizure onset in both animal models (Bragin et al 2005) and human temporal lobe epilepsy (Jirsch et al 2006), suggesting an even more direct link between the two phenomena. In vitro studies of HFO have shown that epileptogenesis (Khalilov et al 2005;Mochovos et al 2008) and ictogenesis (Dzhala and Staley 2003a;Khoshravani et al 2005;Lasztóczi et al 2004) are dependent on HFOs.…”

“…Although the direct excitatory action of GABA has been demonstrated in the neonatal brain (postnatal days Ͻ8) (Khazipov et al 2004;Rivera et al 1999;Tyzio et al 2007), other more complex ways of GABAergic excitation have been established in adult animals and in human epileptic brain (Cohen et al 2002;Epsztein et al 2006;Fujiwara-Tsukamoto et al 2003Kaila et al 1997;Lamsa and Kaila 1997;Marty and Llano 2005;Perez Velazquez 2003;Staley et al 1995). Transitory between neonatal and adult, slices from juvenile (P10-13) rat hippocampus are frequently used in experimental epilepsy research as they are more susceptible to develop seizures than slices from adults (Heinemann et al 1991;Köhling et al 2000;Lasztóczi et al 2004). Interestingly, experimental data supported either excitatory (Dhzala and Staley 2003b;Khazipov et al 2004) or inhibitory/shunting (Rivera et al 1999;Tyzio et al 2007) actions of GABAergic transmission at this age.…”

“…How synchronized activation of large neuronal populations-reflected by the large-amplitude EEG signal of seizures-is brought about is a question of high theoretical and clinical importance. In vivo high-frequency oscillations (HFOs) Ͼ200 Hz preferentially occur at the seizure onset (Bragin et al 2005;Jirsch et al 2006), a feature manifested in vitro (Dzhala and Staley 2003a;Khoshravani et al 2005;Lasztóczi et al 2004). This temporal alignment of HFOs and transition to seizures suggests a causal link between the two phenomena (Bragin et al 2000(Bragin et al , 2002Jirsch et al 2006;Lasztóczi et al 2004).…”

“…In vivo high-frequency oscillations (HFOs) Ͼ200 Hz preferentially occur at the seizure onset (Bragin et al 2005;Jirsch et al 2006), a feature manifested in vitro (Dzhala and Staley 2003a;Khoshravani et al 2005;Lasztóczi et al 2004). This temporal alignment of HFOs and transition to seizures suggests a causal link between the two phenomena (Bragin et al 2000(Bragin et al , 2002Jirsch et al 2006;Lasztóczi et al 2004). HFOs are linked to hyperexcitability and synchrony of neuronal networks, the two hallmarks of epileptiform activity (Le Van Quyen et al 2006;McCormick and Contreras 2001;Perez Velazquez and Carlen 2000;Traub et al 2001).…”

“…Epileptic seizures manifest as uncontrolled limb movements, loss of consciousness and posture, and high-amplitude electroencephalographic (EEG) signals with complex dynamics (Dikanev et al 2005;Jirsch et al 2006;Schiff et al 2000;Worrell et al 2004). How synchronized activation of large neuronal populations-reflected by the large-amplitude EEG signal of seizures-is brought about is a question of high theoretical and clinical importance.…”