Inflammation may trigger anxiety-like behavior by changing how brain immune cells interact with neurons involved in dopamine signaling. Digest
Many people experience anxiety or a loss of drive during illness, yet how signals from the immune system alter brain activity remains poorly understood. In a new study, scientists explored whether immune activation changes how microglia (the brain's resident immune cells) interact with neurons that respond to dopamine, a key chemical messenger that shapes how the brain processes motivation and behavior. They focused on a region called the nucleus accumbens, which plays a central role in regulating these functions.
Adult male mice received a single injection of lipopolysaccharide, a bacterial molecule that causes short‑term inflammation, or a saline (saltwater) control injection. Twelve hours later, the mice underwent behavioral tests that assess anxiety and social behavior.
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The findings showed that even short-term inflammation was sufficient to alter both behavior and brain cell function:
- Mice treated with lipopolysaccharide showed more anxiety‑like behavior, spending less time in open or light areas, and displayed reduced movement consistent with sickness-related fatigue.
- In the nucleus accumbens, fewer dopamine D1 receptor neurons showed signs of activity.
- Electrical recordings showed that these D1 neurons received fewer activating inputs and weaker inhibitory signals from surrounding cells.
- When neurons were grown together with microglia in the lab, their responses to dopamine and glutamate (major neurotransmitter that activates neurons) were dampened, indicating that microglia can directly lower neuron responsiveness.
- Microglia became more active and removed more fragments of nearby neurons, particularly parts involved in sending activating signals, although their overall number did not change.
The results suggest that inflammation makes microglia more active in trimming connections between nerve cells in the nucleus accumbens. This reduction in activating input to dopamine-responsive neurons limits their role in controlling movement, emotion, and motivation, which could underlie the anxiety and sluggishness often seen during illness.
While this study focused on short‑term inflammation in male mice, it offers a detailed picture of how the immune system can reshape brain circuitry to influence mood. The results should not be extrapolated to chronic inflammation, and future work is needed to test responses in females, which may differ due to sex-related differences in hormones and immune system regulation. In episode #41, Dr. Charles Raison explains why we may have evolved immune-mediated mood changes in the first place, a hypothesis he calls the "Pathogen Host Defense" theory of depression.