Fractalkine receptor (CX3CR1) is expressed in microglial cells and its ligand CX3CL1 is expressed in neurons. To analyse the potential role of CX3CL1-CX3CR1 signaling in neuron-microglia interaction, we performed patch clamp recordings in hippocampal slices from developing CX3CR1^+/GFP and CX3CR1^{GFP /GFP} mice between 1^th and 6^th postnatal week, to study functional and morphological properties of developing microglia. In addition, through fluorescence monitoring, we analysed the ability of microglial cells to rearrange ramification in response to ATP pressure applications.

Microglia displayed several voltage-activated currents, including voltage dependent outward K⁺ current, which was abolished by 4-Aminopyridine (2 mM). Outward K⁺ currents showed a developmental profile, with a peak during the second and third postnatal week, then gradually disappeared with age. Microglia also displayed outward rectifying currents elicited by osmotic stress. These currents, likely due to stretch-activated channels, were carried by Cl^- ions and were time and Ca²⁺-dependent; consistently they were reduced by specific blockers flufenamic acid, DIDS, IAA-94. Stretch currents were irreversibly reduced by acute treatment with CX3CL1.

In microglial cells from CX3CR1GFP/GFP mice the number of cells showing voltage dependent outward K+ current was considerably smaller compared to CX3CR1 ^+/GFP. In addition, CX3CR1^GFP/GFP microglia showed a less ramified morphology and a slower rearrangement in response to ATP stimulation.

In conclusion, the expression of CX3CR1 influences functional properties and morphology of microglial cells, pointing to a role of CX3CL1-CX3CR1 signaling in the function of microglia during brain development