Optogenetic Activation of Astrocytes-Effects on Neuronal Network Function.

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

doi:10.3390/ijms22179613

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.

Highlights

Astrocytes play an integral role in the maintenance and regulation of neural networks in the brain
We further found that optogenetic stimulation of hippocampal astrocytes did not affect amplitudes of spontaneous currents in neurons, with no difference before and after the optogenetic stimulation in distribution of EPSCs amplitudes at all stimulation protocols (n = 4, p > 0.05, Mann–Whitney U test)
We discovered that continuous light stimulation with t = 5 s led to non-significant changes in sEPSC frequency compared to baseline level value

Summary

Introduction

Astrocytes play an integral role in the maintenance and regulation of neural networks in the brain. They are able to influence neuronal activity by regulating the extracellular concentration of potassium ions, as well as neurotransmitters, due to the expression on their membrane of a large number of transporters of electrogenic transmitters such as glutamate [1,2], gamma-aminobutyric acid [3,4], and glycine [5,6]. Astrocytes act on neuronal receptors, modulating neuronal excitability, synaptic transmission, and synaptic plasticity. The ability of astrocytes to release glutamate allows regulation of the function of NMDA receptors, thereby controlling the excitation of neuronal network [9]

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Results

Conclusion