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Transcranial Electrical Brain Stimulation in Alert Rodents
Published on: November 2, 2017
Electrified microglia: Impact of direct current stimulation on diverse properties of the most versatile brain cell
Anne-Kathrin Gellner1, Janine Reis2, Bernd L Fiebich3
1Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany; Department of Psychiatry and Psychotherapy, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Background:
Transcranial direct current stimulation [(t)DCS], modulates cortical excitability and promotes neuroplasticity. Microglia has been identified to respond to electrical currents as well as neuronal activity, but its response to DCS is mostly unknown.
Objective:
This study addresses effects of DCS applied in vivo to the sensorimotor cortex on physiological microglia properties and neuron-microglia communication.
Methods:
Time lapse in vivo 2-photon microscopy in anaesthetized mice was timely coupled with DCS of the sensorimotor cortex to observe microglia dynamics on a population-based and single cell level. Neuron-microglia communication during DCS was investigated in mice with a functional knock out of the fractalkine receptor CX3CR1. Moreover, the role of voltage gated microglial channels and DCS effects on phagocytosis were studied.
Results:
DCS promoted several physiological microglia properties, depending on the glial activation state and stimulation intensity. On a single cell level, process motility was predominantly enhanced in ramified cells whereas horizontal soma movement and galvanotaxis was pronounced in reactive microglia. Blockage of voltage sensitive microglial channels suppressed DCS effects in vivo and in vitro. Microglial motility changes were partially driven by the fractalkine signaling pathway. Moreover, phagocytosis increased after DCS in vitro.
Conclusion:
Microglia dynamics are rapidly influenced by DCS. This is the first in vivo demonstration of a direct effect of electrical currents on microglia and indirect effects potentially driven by neuronal activity via the fractalkine pathway.
Insights
Transcranial direct current stimulation (tDCS) rapidly influences microglia dynamics, affecting their movement and communication. This study reveals direct electrical effects on microglia, modulated by neuronal activity and fractalkine signaling.
Area of Science:
- Neuroscience
- Cell Biology
- Neuroimmunology
Background:
- Transcranial direct current stimulation (tDCS) modulates brain activity and neuroplasticity.
- Microglia, the brain's immune cells, respond to electrical stimuli and neuronal activity, but their specific response to tDCS is largely unknown.
Purpose of the Study:
- To investigate the in vivo effects of tDCS on microglia physiology and neuron-microglia communication.
- To elucidate the role of voltage-gated channels and fractalkine signaling in microglia's response to tDCS.
Main Methods:
- Utilized time-lapse in vivo two-photon microscopy in anesthetized mice during sensorimotor cortex tDCS.
- Examined neuron-microglia communication using CX3CR1 knockout mice.
- Assessed the impact of blocking voltage-gated microglial channels and studied phagocytosis in vitro.
Main Results:
- tDCS altered microglia properties, with effects varying by glial activation state and stimulation intensity.
- Single-cell analysis showed enhanced process motility in ramified microglia and increased soma movement/galvanotaxis in reactive microglia.
- Blocking voltage-gated channels suppressed tDCS effects, and fractalkine signaling partially mediated motility changes. Phagocytosis increased post-tDCS in vitro.
Conclusions:
- Microglia dynamics are rapidly influenced by tDCS, demonstrating a direct effect of electrical currents on these cells.
- The study provides the first in vivo evidence of tDCS directly impacting microglia, with indirect effects mediated by neuronal activity via the fractalkine pathway.
