Article
Intracellular recordings in patients with temporal lobe epilepsy
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Published: | June 9, 2017 |
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Objective: Resection of the temporomesial structures is a well-established treatment for refractory temporal lobe epilepsy (TLE). The benefit of this procedure was shown repeatedly, yet, the precise extent of the epileptogenic zone and its cellular pathomechanisms are insufficiently understood. In this study we investigated spontaneous and chemically induced excitatory postsynaptic potentials (EPSPs) in slices of the human hippocampus and temporal lobe and compared the results with clinical findings.
Methods: From 08/2015 to 10/2016 we recorded intracellular activity using patch clamp technique in 23 patients with TLE who underwent neurosurgical resection of the putative epileptogenic zone. In 5 of the 23 patients an invasive stereotactic EEG-monitoring was conducted preoperatively to determine the seizure onset zone. Slices (350mm) of the hippocampus and temporal neocortex were prepared directly after surgical removal. A low magnesium solution was used to induce seizure-like activity in 19 slices. EPSPs were recorded in artificial cerebrospinal fluid and after infusion of the low magnesium solution in pyramidal cells of the CA1/subiculum region and of the temporal neocortex. Statistical comparisons were performed with ANOVA using SPSS 23.0.
Results: Single-cell recordings from 22 neurons were analyzed in this setting. Under baseline conditions, 2 neurons showed action potentials spontaneously. After infusion of the low magnesium solution, action potentials were detected in 16 neurons (p<0.001). The amplitude and frequency of EPSPs not leading to an action potential did not differ between the conditions (1.06mV vs. 1.07mV and 1.42Hz vs. 1.23Hz). When administered, an AMPA receptor antagonist suppressed the EPSPs. All five patients with preceding invasive monitoring showed ictal activity in vivo and spontaneous and/or inducible action potentials with spiking frequencies up to 270Hz in the corresponding region in vitro.
Conclusion: In vitro ictal-like activity in the human temporomesial structures seems to depend on AMPAR-driven action potentials and not on subthreshold EPSPs. Comparisons with in vivo data from invasive electrophysiological monitoring suggest that the observed fast spiking action potentials correspond to ictal activity in these structures.