Mast cells on the mind: new insights and opportunities

•Mast cells (MCs) are brain-resident immune cells that serve both as sensors and effectors in communication among nervous, vascular and immune systems.•MCs lie on the brain side of the blood–brain barrier (BBB) and communicate with neurons, glia, blood vessels, and other hematopoietic cells via their neuroactive prestored and newly synthesized chemicals.•Although small in number, MCs exert powerful effects because they are first responders that act as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation.•MCs both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotionality.•New experimental tools enabling isolation of brain MCs, manipulation of MCs or of their products, and measurement of MC products in very small brain volumes present unprecedented opportunities for examining these enigmatic cells, both during development and adulthood.

Mast cells (MCs) are both sensors and effectors in communication among nervous, vascular, and immune systems. In the brain, they reside on the brain side of the blood–brain barrier (BBB), and interact with neurons, glia, blood vessels, and other hematopoietic cells via their neuroactive prestored and newly synthesized chemicals. They are first responders, acting as catalysts and recruiters to initiate, amplify, and prolong other immune and nervous responses upon activation. MCs both promote deleterious outcomes in brain function and contribute to normative behavioral functioning, particularly cognition and emotionality. New experimental tools enabling isolation of brain MCs, manipulation of MCs or their products, and measurement of MC products in very small brain volumes present unprecedented opportunities for examining these enigmatic cells.