gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Electrophysiological and live-imaging studies of synaptic signaling in temporal cortex resectates from epilepsy patients – in search of a mechanism for memory impairment

Elektrophysiologische und live-imaging Untersuchungen der synaptischen Übertragung in-vitro im temporalen Cortex aus Epilepsie-chirurgischen Eingriffen – auf der Suche nach Mechanismen für die Gedächtnisstörung

Meeting Abstract

  • presenting/speaker Anna Maslarova - Universitätsklinikum Erlangen, Neurochirurgie, Erlangen, Deutschland
  • Sarah Schröter - Klinikum Osnabrück, Osnabrücker Zentrum für muskuloskelettale Chirurgie, Osnabrück, Deutschland
  • Simon Aicher - Universitätsklinikum Erlangen, Neurochirurgie, Erlangen, Deutschland
  • Thomas Kinfe - Universitätsklinikum Erlangen, Neurochirurgie, Erlangen, Deutschland
  • Michael Buchfelder - Universitätsklinikum Erlangen, Neurochirurgie, Erlangen, Deutschland
  • Andreas Stadlbauer - Universitätsklinikum Erlangen, Neurochirurgie, Erlangen, Deutschland
  • Sebastian Brandner - Universitätsklinikum Erlangen, Neurochirurgie, Erlangen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV024

doi: 10.3205/22dgnc025, urn:nbn:de:0183-22dgnc0253

Published: May 25, 2022

© 2022 Maslarova et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Memory impairment is a common comorbidity in chronic temporal lobe epilepsy. Whereas recurrent seizures in the mesial temporal structures and antiepileptic drugs may disrupt memory function, the exact neurobiological mechanism behind memory impairment remains elusive. Memory formation involves activity-dependent modification of synaptic weights. Thus, long-term potentiation (LTP) of synaptic transmission by electrical stimulation is an efficient model for studying memory at the neurophysiological level and requires intact glutamatergic signaling. We were therefore interested in studying LTP and glutamate signaling in the human cortex of epilepsy patients.

Methods: We performed field potential recordings in acute cortical slices from resection specimens obtained during surgery for drug-resistant temporal lobe epilepsy. LTP-induction upon a standardized theta-burst stimulation protocol was asessed. Some slices were additionally incubated with the fluorescent nanosensor iGluu, which undergoes changes in fluorescence intensity upon binding to extracellular glutamate.

Results: LTP induction was weak and unreliable in the human temporal cortex. In some slices, theta-burst stimulation lead to paradoxical induction of long-term depression of synaptic plasticity. By contrast, LTP was enhanced in the presence of a glucocorticoid receptor blocker. In slices subjected to fluorescence imaging, we observed transient changes in iGluu fluorescence signal intensity upon electrical stimulation, indicative of successful detection of glutamate release.

Conclusion: LTP induction in acute slices presents an opportunity to study the mechanisms underlying memory impairment in the human cortex. This model is a valuable complement to data from non-invasive recording modalities and stereo EEG, as it offers the unique possibility of pharmacological manipulation of synapses. Besides, we demonstrate for the first time that extracellular glutamate release can be monitored in human cortical slices with the iGluu nanosensor. In future experiments, this method will allow to gain insights on how glutamate dynamics affects human synaptic plasticity.