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Updated: May 13, 2026
In Vivo Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus
Published on: July 6, 2022
Microglia, seen from the CX3CR1 angle
Yochai Wolf1, Simon Yona, Ki-Wook Kim
1Department of Immunology, The Weizmann Institute of Science Rehovot, Israel.
Abstract:
Microglial cells in brain and spinal cord are characterized by high expression of the chemokine receptor CX3CR1. Expression of the sole CX3CR1 ligand, the membrane-tethered and sheddable chemokine CX3CL1/fractalkine, is restricted in the brain parenchyma to selected neurons. Here we summarize our current understanding of the physiological role of CX3CR1 for microglia function and the CX3C axis in microglial/neuronal crosstalk in homeostasis and under challenge. Moreover, we will discuss the efforts of our laboratory and others to exploit CX3CR1 promoter activity for the visualization and genetic manipulation of microglia to probe their functional contributions in the central nerve system (CNS) context.
Insights
Microglia utilize the CX3CR1 receptor to interact with neurons via CX3CL1/fractalkine. This CX3C axis is crucial for brain homeostasis and response to injury, with CX3CR1 promoter activity aiding microglia research.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells, the primary immune cells of the central nervous system (CNS), express high levels of the chemokine receptor CX3CR1.
- The only known ligand for CX3CR1 is CX3CL1/fractalkine, a chemokine primarily expressed by neurons in the brain parenchyma.
- The CX3C axis, comprising CX3CR1 and CX3CL1, plays a significant role in modulating microglial function and neuronal communication.
Purpose of the Study:
- To summarize the physiological functions of CX3CR1 in microglia.
- To elucidate the role of the CX3C axis in microglial-neuronal crosstalk during CNS homeostasis and disease.
- To review strategies for utilizing CX3CR1 promoter activity for microglia research in the CNS.
Main Methods:
- Literature review and synthesis of existing research on the CX3CR1/CX3CL1 axis.
- Analysis of studies investigating microglial function and neuronal interactions.
- Discussion of genetic and imaging techniques targeting the CX3CR1 promoter.
Main Results:
- CX3CR1 signaling is integral to microglial homeostasis and their communication with neurons.
- The CX3C axis influences microglial responses under both normal physiological conditions and pathological challenges.
- Exploiting the CX3CR1 promoter enables targeted visualization and genetic manipulation of microglia.
Conclusions:
- The CX3CR1-CX3CL1 axis is a key regulator of microglial-neuronal interactions in the CNS.
- Understanding this axis is vital for comprehending brain function and disease.
- CX3CR1-based tools offer promising avenues for advancing microglia-focused neuroscience research.
