Abstract
We have shown in mice there are two cell lineages that give rise to microglia with distinct ontogenies; Hoxb8 microglia and non-Hoxb8 microglia. Disruption of Hoxb8 or ablation of the Hoxb8 cell lineage gives rise to both chronic anxiety and OCSD-like behavior (trichotillomania, compulsive pathological overgrooming leading to lesions at the sites of overgrooming). There is a strong sex bias for both behavioral pathologies, with females showing much more aggressive disease. By cell transplantation of purified, cell sorted Hoxb8 microglia progenitors derived from Wt or Hoxb8 mutant mice we were able to demonstrate causation of defective Hoxb8 microglia for both behavioral pathologies. More recently we have demonstrated that optogenetic activation of Hoxb8 microglia in specific regions of the brain induces higher levels of anxiety, grooming or both. Further, these experiments have demonstrated that Hoxb8 microglia function to reduce anxiety and grooming (function as brakes) whereas non-Hoxb8 microglia function to increase these behaviors (function as an accelerator). Now we know why mammals have two populations of microglia.