Anxiety disorders, including obsessive compulsive spectrum disorder (OCSD), affect nearly a fifth of Americans, but the brain mechanisms that underlie anxiety remain unclear.

Now, scientists at the University of Utah Health have identified specific populations of brain cells that appear to be involved in anxiety-like behaviors, paving the way for better understanding and management of these conditions.

Surprisingly, the cells aren’t neurons, but a category of brain cells called microglia, which act as the brain’s cleanup crew. Microglia help clear germs and debris from the brain, which is vital for overall brain function, but these cells aren’t generally thought to contribute to complex processes like anxiety.

The team of scientists found that microglia seem to be able to communicate with their neuron neighbors, affecting distinct regions of the brain to influence complicated behaviors.

The researchers had previously noticed that mice with a mutation in a gene called Hoxb8 tended to display anxiety and OCSD-like behaviors, like excessive grooming. This same lab had also discovered that these behaviors depended on whether the mutation was present in microglia.

The researchers suspected that the microglia might be communicating with specific brain regions or neural circuits to drive these behaviors, but they didn’t know which regions might be responsible.

To pinpoint which cells might be involved in anxiety-like behaviors, the researchers needed a way to affect the activity of microglia in specific regions of the brain – while leaving the neurons around them untouched. They used a technique called optogenetics to first ensure that microglia, but not neurons, would change their activity when exposed to laser light. Then, they shone a laser on different small brain regions, targeting groups of microglia with pinpoint precision.

Using this technique, researchers were able to identify multiple parts of the brain that regulated different anxiety-like behaviors. Shining a laser on one brain region caused increased grooming, and affecting the microglia in another region increased other anxiety-like behaviors. When the laser was turned off, the mice went back to behaving as normal.

Studying these behaviors in mice enabled the researchers to investigate complex behaviors, like anxiety, that only occur in complex animals, while using genetic tools to narrow down on the brain regions responsible.

By identifying new contributors to anxiety-like behaviors, this work may ultimately help us understand and treat anxiety disorders.