Microglia-neuron communication in normal and diseased brain
The long-term goal of my lab is to understand microglia-neuron communication in the brain. Microglia are the principal immune-response cells in the central nervous system. Resting microglia constantly survey the microenvironment in the normal brain. Upon brain dysfunction, microglia are activated and exert detrimental or beneficial effects on the surrounding neurons. Microglia have remarkably fast and dynamic activities in both the normal and pathological brain. An exciting possibility is that they are communicating with neurons through ion channel mechanisms. In neuronal circuits, microglia are assumed to be crucial to synaptic pruning and plasticity, yet no direct evidence has been identified. Microglia are strongly activated in pathological conditions such as pain, stroke and neurodegeneration, however, the molecular mechanisms for microglial activation and function in brain diseases are still controversial.
Overall, we are interested in three interrelated topics on microglia-neuron communication (Eyo and Wu, 2013): (1) The ion channel mechanism of microglia-neuron communication; (2) Microglia in synaptic function; and (3) Microglia’s contribution to neuropathic pain. We have been exploring microglia chemotaxis (Wu et al., 2007), microglia in synaptic plasticity (Wu and Zhuo, 2008), as well as an unique microglial voltage-gated proton channel, Hv1, in the brain (Wu et al., 2012). Taking Hv1 proton channel as an entry point, our initial project will study direct communication from microglia to neurons through microglial Hv1. We will then explore how microglia function in neuronal circuits under normal and pain conditions. The results from our studies would advance the understanding of microglia function in the brain and provide therapeutic targets for neuropathic pain treatment.