A study led by researchers in pediatrics and child neurology at the University of Louisville School of Medicine reveals how specific signaling mechanisms in the brain’s immune cells, microglia, can modulate anxiety and grooming behaviors. These behaviors are core symptoms of autism and obsessive-compulsive spectrum disorders.
The research was conducted by Naveen Nagarajan, an assistant professor in the UofL Department of Pediatrics, in collaboration with University of Utah geneticist Mario Capecchi, winner of the 2007 Nobel Prize in Physiology or Medicine. molecular psychiatryNature Publishing Journal, one of the top scientific journals.
This study focuses on Hoxb8 microglia, a specialized group of brain immune cells. These cells use calcium signaling to help regulate anxiety and grooming behavior in mice. Nagarajan’s previous research showed that healthy mice can produce these behaviors when activated.
Mouse that lacks Hoxb8 These genes predispose them to extreme anxiety and pathological over-grooming. This condition is observed in humans suffering from chronic anxiety disorder (nearly 4.4% of the world’s population) and obsessive-compulsive disorder, which affects nearly 1% to 3% worldwide. The second phase of the study investigated what signals within these cells drive such behavior.
The researchers used optogenetics, a technique that activates cells with light, to increase calcium levels in Hoxb8 microglia in mice. To measure these tiny calcium signals within 10-15 μm microglial cells, Nagarajan used a weighing miniature microscope, or miniscope, weighing 2.4 g to record the signals for the first time in awake, behaving mice.
Increased calcium levels caused anxiety and grooming behavior. They also Hoxb8 Genes lose the ability to regulate calcium, resulting in a constant influx of calcium, causing chronic anxiety and compulsive over-grooming.
To test whether calcium itself is the driving force behind these behaviors, Nagarajan and Capecchi used a sophisticated genetic technique to inhibit calcium entry into Hoxb8 microglia, the light-activated channel ChRmine. This manipulation prevented anxiety-related behaviors and confirmed a direct correlation between calcium and anxiety-induced behaviors.
The discovery of these specific calcium signals opens opportunities for future treatments for anxiety-related disorders, the ability to identify calcium homeostasis when diagnosing neuropsychiatric disorders, and new understanding of how immune cells influence brain circuits during development.
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Reference magazines:
Nagarajan, N. and Capecchi, MR (2026) Microglia use calcium signaling to respond to and elicit anxiety and grooming in mice. molecular psychiatry. DOI:10.1038/s41380-026-03572-w. https://www.nature.com/articles/s41380-026-03572-w.
