Real-time imaging of glutamate transients in the extracellular space of acute human brain slices using a single-wavelength glutamate fluorescence nanosensor

Sebastian Brandner, Simon Aicher, Sarah Schroeter, Izabela Swierzy, Thomas M Kinfe, Michael Buchfelder, Anna Maslarova, Andreas Stadlbauer

Research output: Journal article (peer-reviewed)Journal article

1 Citation (Scopus)

Abstract

Glutamate is the most important excitatory neurotransmitter in the brain. The ability to assess glutamate release and re-uptake with high spatial and temporal resolution is crucial to understand the involvement of this primary excitatory neurotransmitter in both normal brain function and different neurological disorders. Real-time imaging of glutamate transients by fluorescent nanosensors has been accomplished in rat brain slices. We performed for the first time single-wavelength glutamate nanosensor imaging in human cortical brain slices obtained from patients who underwent epilepsy surgery. The glutamate fluorescence nanosensor signals of the electrically stimulated human cortical brain slices showed steep intensity increase followed by an exponential decrease. The spatial distribution and the time course of the signal were in good agreement with the position of the stimulation electrode and the dynamics of the electrical stimulation, respectively. Pharmacological manipulation of glutamate release and reuptake was associated with corresponding changes in the glutamate fluorescence nanosensor signals. We demonstrated that the recently developed fluorescent nanosensors for glutamate allow to detect neuronal activity in acute human cortical brain slices with high spatiotemporal precision. Future application to tissue samples from different pathologies may provide new insights into pathophysiology without the limitations of an animal model.

Original languageEnglish
Article number3926
Pages (from-to)3926
JournalScientific Reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022

Keywords

  • Animals
  • Brain/physiology
  • Extracellular Space
  • Glutamic Acid/pharmacology
  • Humans
  • Neurons
  • Neurotransmitter Agents
  • Rats

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