A specific group of microglia, called Hoxb8 microglia, seem to be able to trigger obsessive grooming anxiety-related behaviors in mice. When researchers used genetic tools combined with precise light-based cell stimulation to temporarily activate Hoxb8 microglia in a healthy mouse, the mice performed grooming and anxiety-like behaviors. But until now, scientists didn’t know what was going on within Hoxb8 microglia cells that trigger these changes. Researchers found that calcium signaling within microglia is pivotal.
High levels of calcium within microglia act as a critical molecular signal that triggers obsessive grooming and anxiety, the researchers found. Calcium ions enable microglia cells to encode and transmit instructions that shape behavioral output. When normal mice performed grooming, freezing in place, or other anxiety-like behaviors, calcium levels spiked in Hoxb8 microglia. When the behaviors stopped, calcium returned to normal levels. In mice with chronic anxiety and OCSD, calcium is always high in Hoxb8 mutant microglia.
To figure out what was going on in microglia during anxiety and grooming behaviors, the research team used a combination of genetic tools and a miniaturized microscope half the size of a fingernail. Calcium signaling caused genetically engineered microglia to light up green, and the mini microscope watched as calcium levels changed within individual microglia cells for the first time in the brain in freely behaving mice.