Nobel Laureate Describes Dogma-Breaking Brain Research

Brain cells called microglia are known to act as immune sentries of the brain, clearing debris and dead cells, and fighting infections. But controlling behavior? That wasn’t part of their job description.

Nobel Prize-winning neurobiologist Mario R. Capecchi, Ph.D., visited The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology on Thursday, delivering a gripping lecture about how his team at the University of Utah discovered that a gene called Hoxb8 influences chronic anxiety and OCD behaviors.

Nobel Laureate Mario R. Capecchi, Ph.D., delivered a distinguished lecture at The Wertheim UF Scripps Institute on April 6, 2023.

“We are suggesting that microglia are controlling very specific behaviors. They are talking to neurons, and the neurons are controlling behavior,” Capecchi said.

Part of the graduate program’s Distinguished Lecture Series, Capecchi’s talk described using the same mouse genetics research methods that earned him the Nobel Prize in 2007, bolstered by newer techniques for controlling the activity of cells, especially optogenetics. Blending these and other methods helped his group show that the gene transcription factor Hoxb8 influences OCD and anxiety behaviors in mice in a surprising way — not within neurons, but within another group of brain cells, microglia.

His team found in 2017 that the brain is populated by two lineages of microglia, those that have Hoxb8, about 30 percent of the microglia, and those that do not, about 70 percent. It appears that the two work in opposition to suppress or accelerate anxiety behaviors.

Despite being a Nobel Laureate, Capecchi has found that breaking scientific dogma can provoke skepticism and even backlash. It drives him to conduct more research.

“I have had people in the field literally insult me,” he told the students. “But the data is there.”

Chronic anxiety affects more than 20 percent of the population, affecting more women than men. Understanding the biology behind it is important, he stressed.

The next stage of his research is investigating which neurons interact with the microglia to direct the OCD-like behaviors and anxiety, and then to discern how the microglia transmit the signals, he said. There’s a correlation with female hormones that needs further explorations, he noted.

“Some neurons express estrogen and some don’t, so it gives us a clue,” he said. “Once we know which neurons, we can do a lot more experiments.”

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