Research in the microglia field has mainly focused on resolving microglia-neuron interactions during development and disease. Our knowledge of microglia in adulthood is limited, even though they are constantly exposed to environmental cues and regularly interact with synapses. We became interested in our initial question: how do anesthetics influence microglia when the overall brain activity is lowered to a minimum?

The extracellular matrix (ECM) landscape is a critical component. The ECM surrounds the cellular landscape of the brain and can be broadly divided into the defined rigid perineuronal net (PNN), which encloses soma and proximal neuronal processes, and the diffuse perisynaptic ECM ECM composition profoundly influences the induction and consolidation of synaptic plasticity and homeostasis The PNN can sterically restrict spine formation and receptor movement, and enhance fast-firing properties due to an altered electrical charge. Microglia are known to express modulators involved in the ECM proteolytic pathway. This expression could be simply due to their surveillance function, requiring local disassembling of the ECM to pass their processes through, or representing targeted intervention to guarantee neuronal network functionality for performing homeostatic plasticity.