Optogenetic activation of astrocytes—effects on neuronal network function

Evgenii Gerasimov, Alexander Erofeev, Anastasia Borodinova, Anastasia Bolshakova, Pavel Balaban, Ilya Bezprozvanny, Olga L. Vlasova

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Optogenetics approach is used widely in neurobiology as it allows control of cellular activity with high spatial and temporal resolution. In most studies, optogenetics is used to control neuronal activity. In the present study optogenetics was used to stimulate astrocytes with the aim to modulate neuronal activity. To achieve this goal, light stimulation was applied to astrocytes expressing a version of ChR2 (ionotropic opsin) or Opto-α1AR (metabotropic opsin). Optimal optogenetic stimulation parameters were determined using patch-clamp recordings of hippocampal pyramidal neurons’ spontaneous activity in brain slices as a readout. It was determined that the greatest increase in the number of spontaneous synaptic currents was observed when astrocytes expressing ChR2(H134R) were activated by 5 s of continuous light. For the astrocytes expressing Opto-α1AR, the greatest response was observed in the pulse stimulation mode (T = 1 s, t = 100 ms). It was also observed that activation of the astrocytic Opto-a1AR but not ChR2 results in an increase of the fEPSP slope in hippocampal neurons. Based on these results, we concluded that Opto-a1AR expressed in hippocampal astrocytes provides an opportunity to modulate the long-term synaptic plasticity optogenetically, and may potentially be used to normalize the synaptic transmission and plasticity defects in a variety of neuropathological conditions, including models of Alzheimer’s disease and other neurodegenerative disorders.

Original languageEnglish (US)
Article number9613
JournalInternational journal of molecular sciences
Volume22
Issue number17
DOIs
StatePublished - Sep 2021

Keywords

  • Astrocytes
  • Channelrhodopsin-2
  • Hippocampal neurons
  • Opto-α1-adrenoreceptor
  • Optogenetics
  • Patch-clamp

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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