Intracellular Study of Human Epileptic Cortex: In Vitro Maintenance of Epileptiform Activity?

Abstract

Intracellular recordings were obtained in the vitro slice preparation from neurons of lateral and mesial temporal cortex removed from human epileptics suffering from intractable temporal lobe seizures. Spontaneous rhythmic synaptic events, which were capable of triggering action potential discharge, were observed in many neurons, particularly in mesial tissue slices. Such activity may reflect the epileptogenic capacity of this human cortex.

Excitatory synaptic potentials in kainic acid-denervated rat CA1 pyramidal neurons

“…The KA lesion has been suggested to exhibit many of the characteristics of the human temporal lobe epileptic lesion, including neuron damage and loss, relative preservation of inhibitory neurons without demonstrable postsynaptic inhibition, and the presence of graded bursts (Nadler et al, 1980a,b;Lothman and Collins, 1981;Cavalheiro et al, 1982;Schwartzkroin and Knowles, 1984;Dichter and Ayala, 1987;Franck et al, 1988;Wheal, 1989). The present data indicate that the sensitivity of the graded bursts to NMDA antagonists may also be another similarity (Avoli and Olivier, 1987).…”

“…kroin and Knowles, 1984;Avoli and Olivier, 1987). These graded bursts are significantly different from the structured bursts associated with acute loss of inhibitory drive, which also demonstrate an associated afterhyperpolarization (Dingledine and Gjerstad, 1980;Johnston and Brown, 198 1;Wheal et al, 1984).…”

“…The study of chronic animal models of epilepsy and human brain tissue slices (Lothman and Collins, 198 1;Pumain, 198 1;Wheal, 1982, 1984;Schwartzkroin et al, 1983;Schwartzkroin and Knowles, 1984;Ashwood et al, 1986;Ashwood and Wheal, 1987;Avoli and Olivier, 1987;Mody and Heinemann, 1987;Franck et al, 1988;Nakajima et al, 199 1;Sloviter, 1991) has revealed new physiological mechanisms underlying bursting activity that were not observed in in vitro models generated by acute convulsants, such as penicillin and bicucilline, which block inhibitory processes (Dingledine and Gjerstad, 1980;Johnston and Brown, 198 1;Wheal et al, 1984). The chronic animal models and abnormal human tissue show less structured and more graded bursting activity than the acute convulsant models.…”

Massive and Specific Dysregulation of Direct Cortical Input to the Hippocampus in Temporal Lobe Epilepsy

“…Second, removal of the affected hippocampus eliminates seizures in 80 -90% of TLE patients exhibiting unilateral mesial temporal lobe sclerosis (Falconer et al, 1964;Ojemann, 1987). Third, stereotypic neuropathology is found in the hippocampus of TLE patients that is recapitulated in animal models of TLE, termed hippocampal sclerosis (Schwartzkroin and Knowles, 1984;Sutula et al, 1988;Houser et al, 1990;French et al, 1993;Mello et al, 1993;Buckmaster and Dudek, 1997). Given that the hippocampus is critical in TLE, are there specific hippocampal circuits which could play a dominant role in the regulation of excitability, and could damaged function in these areas be particularly significant in the epileptic brain?…”

GABAergic Synaptic Inhibition Is Reduced before Seizure Onset in a Genetic Model of Cortical Malformation

“…Given the complexity of these events, it is not surprising that neurons in a malformed cortex may harbor aberrant physiological features that could contribute to the generation of seizures and epilepsy (Barkovich and Raybaud, 2004;Najm et al, 2004;Guerrini and Filippi, 2005). Studies performed on human brain tissue from surgical resections indicate that dysplastic tissue is hyperexcitable compared with surrounding eloquent tissue (Schwartzkroin and Knowles, 1984;Reid and Palovcik, 1989;Mattia et al, 1995;Avoli et al, 1999Avoli et al, , 2003. However, the inherent limitations of experiments involving human tissue and the inability to assess neural function before seizure onset have limited progress in characterizing the cause(s) of epileptogenesis.…”