Challenging Neuroscience Assumptions

University of Utah Health scientists have discovered that microglia, a minor type of cells in the brain, play a crucial role in controlling anxiety-related behaviors. The findings challenge the prevailing belief that neurons are solely responsible for behavior regulation.

“A small amount of anxiety is good,” says U Nobel Laureate Mario Capecchi, the senior author of the study. “Anxiety motivates us, spurs us on, and gives us that extra bit of push that says, ‘I can.’ But a large dose of anxiety overwhelms us. We become mentally paralyzed, the heart beats faster, we sweat, and confusion settles in our minds.”

The study used mice exhibiting obsessive-compulsive spectrum disorder (OCSD)-like behaviors, characterized by excessive self-grooming. Previous research had identified a mutation in the gene Hoxb8 as a cause of chronic anxiety and excessive grooming in these mice. The surprising discovery in this study was that microglia, which make up only 10 percent of brain cells, were responsible for these behaviors, contrary to the perception that they primarily function as “trash collectors” for dying neurons.

Using optogenetics, a technique combining genetic engineering and laser light, the researchers stimulated specific populations of microglia in the brain. The results were astonishing—activating certain microglia populations induced anxiety-related behaviors, while stimulating others caused the mice to groom themselves excessively. The study demonstrated that microglia and neurons communicate with each other, with the former influencing the latter to generate distinct behaviors.

“Conventionally, it is thought that only neurons can generate behaviors,” says lead author Naveen Nagarajan. “The current findings shed light on a second way that the brain generates behaviors using microglia.”

Moreover, the researchers identified a delicate balance between two populations of microglia. While Hoxb8 microglia acted as a brake, preventing anxiety and OCSD-like behaviors, non-Hoxb8 microglia acted as an accelerator, driving the onset of these behaviors. Imbalance between these populations could lead to pathological conditions.

Understanding the location and type of microglia could help us fine-tune our understanding of anxiety and OCSD behaviors. By deciphering the intricate communication between microglia and neurons, scientists hope to identify potential therapeutic targets for managing excessive anxiety in patients.

“This work is unique and has challenged the current dogma about the role of microglia function in the brain,” Nagarajan concludes.