Application of chemogenetics and optogenetics to dissect brain-immune interactions

For many years, the complexity and multifactorial nature of brain-immune interactions limited our ability to dissect their underlying mechanisms. An especially challenging question was how the brain controls immunity, since the repertoire of techniques to control the brain’s activity was extremely limited. New tools, such as optogenetics and chemogenetics (e.g., DREADDs), developed over the last decade, opened new frontiers in neuroscience with major implications for neuroimmunology. These tools enable mapping the causal effects of activating/attenuating defined neurons in the brain, on the immune system. Here, we present a detailed experimental protocol for the analysis of brain-immune interactions, based on chemogenetic or optogenetic manipulation of defined neuronal populations in the brain, and the subsequent analysis of immune cells. Such detailed and systematic dissection of brain-immune interactions has the potential to revolutionize our understanding of how mental and neurological states affect health and disease.