RT Journal Article SR Electronic T1 Regulation of Physical Microglia–Neuron Interactions by Fractalkine Signaling after Status Epilepticus JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0209-16.2016 DO 10.1523/ENEURO.0209-16.2016 VO 3 IS 6 A1 Ukpong B. Eyo A1 Jiyun Peng A1 Madhuvika Murugan A1 Mingshu Mo A1 Almin Lalani A1 Ping Xie A1 Pingyi Xu A1 David J. Margolis A1 Long-Jun Wu YR 2016 UL http://www.eneuro.org/content/3/6/ENEURO.0209-16.2016.abstract AB Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia–neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid– or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice. Interestingly, a deficiency of the fractalkine receptor (CX3CR1) decreased MPCs, whereas fractalkine (CX3CL1) treatment increased MPCs, suggesting that fractalkine signaling is a critical regulator of these microglia–neuron interactions. Furthermore, we found that interleukin-1β was necessary and sufficient to trigger CX3CR1-dependent MPCs. Finally, we show that a deficiency in fractalkine signaling corresponds with increased seizure phenotypes. Together, our results identify the neuroglial CX3CL1–CX3CR1 communication axis as a modulator of potentially neuroprotective microglia–neuron physical interactions during conditions of neuronal hyperactivity.