Authors: Naveen Nagarajan; Mario R. Capecchi · Research

How Do Brain Immune Cells Influence Anxiety and Grooming Behaviors?

Researchers discover how a specific type of brain immune cell can trigger anxiety and excessive grooming when activated in certain brain regions.

Source: Nagarajan, N., & Capecchi, M. R. (2024). Optogenetic stimulation of mouse Hoxb8 microglia in specific regions of the brain induces anxiety, grooming, or both. Molecular Psychiatry, 29, 1726-1740. https://doi.org/10.1038/s41380-023-02019-w

What you need to know

  • Researchers used light to activate a specific type of brain immune cell called Hoxb8 microglia in different brain regions of mice
  • Activating Hoxb8 microglia in certain brain areas triggered anxiety-like behaviors or excessive grooming
  • The effects depended on which brain region was stimulated - some areas induced anxiety, others grooming, and some both
  • This suggests Hoxb8 microglia play an important role in regulating anxiety and grooming behaviors
  • Understanding how these immune cells influence behavior could lead to new treatments for anxiety disorders and related conditions

A new way to study brain immune cells and behavior

Our brains contain immune cells called microglia that help protect and maintain brain health. Researchers have found that a specific type of microglia, called Hoxb8 microglia, may play an important role in regulating anxiety and grooming behaviors. However, studying exactly how these cells influence behavior has been challenging.

In this study, scientists used an advanced technique called optogenetics to activate Hoxb8 microglia in specific brain regions of mice. Optogenetics involves inserting light-sensitive proteins into cells, allowing researchers to turn them on or off using light. This gave the researchers precise control over when and where to activate the Hoxb8 microglia.

Activating brain immune cells triggers anxiety and grooming

The researchers found that activating Hoxb8 microglia in certain brain areas caused mice to display anxiety-like behaviors or excessive grooming. Interestingly, the effects depended on which brain region was stimulated:

  • Activating Hoxb8 microglia in the dorsomedial striatum or medial prefrontal cortex triggered grooming behaviors
  • Stimulation in the basolateral amygdala or central amygdala induced anxiety-like behaviors
  • Activation in the ventral CA1 region of the hippocampus caused both anxiety and grooming, as well as freezing behavior

This suggests that Hoxb8 microglia in different brain regions play distinct roles in regulating anxiety and grooming. The researchers were able to reliably induce these behaviors by stimulating the cells for just a few minutes. When the stimulation stopped, the behaviors quickly returned to normal.

How do the immune cells influence behavior?

The study provides strong evidence that activating Hoxb8 microglia can rapidly trigger anxiety and grooming behaviors. But how exactly do these immune cells communicate with neurons to influence behavior?

The researchers found that stimulating Hoxb8 microglia caused nearby neurons to become more active. Specifically, the neurons showed increased firing of electrical signals and changes in gene activity. This suggests the microglia are able to directly modulate neuronal activity when activated.

However, many questions remain about the precise mechanisms involved. The researchers propose that Hoxb8 microglia may release chemical signals that affect nearby neurons when activated. Alternatively, the electrical stimulation of the microglia may directly influence neuronal circuits. Further research will be needed to unravel the complex interactions between these immune cells and neurons.

An unexpected twist - opposing roles for different microglia

In an intriguing finding, the researchers discovered that simultaneously activating both Hoxb8 microglia and another type of microglia actually prevented the anxiety and grooming behaviors from occurring.

This suggests the two types of microglia may play opposing roles - with Hoxb8 microglia promoting anxiety/grooming behaviors and the other type inhibiting them. The researchers propose this system may allow for fine-tuned control over these behaviors.

This unexpected result highlights how complex the interactions between different brain cell types can be. It also provides a potential explanation for why the brain maintains two distinct populations of microglia.

Implications for understanding anxiety disorders

Anxiety disorders affect hundreds of millions of people worldwide. However, we still have a limited understanding of the brain mechanisms underlying anxiety.

This research provides new insight into how a specific type of brain immune cell can rapidly trigger anxiety-like behaviors when activated in certain brain regions. It also demonstrates a direct link between these immune cells and the neural circuits involved in anxiety and repetitive behaviors like grooming.

Understanding these mechanisms could potentially lead to new treatment approaches for anxiety disorders and related conditions like obsessive-compulsive disorder. For example, drugs that modulate the activity of specific microglia populations may be able to reduce anxiety symptoms.

Looking ahead - key questions for future research

While this study provides important new insights, it also raises many questions for future investigation:

  • What specific signals do activated Hoxb8 microglia use to communicate with neurons?
  • Are the same or different mechanisms involved in different brain regions?
  • Which specific types of neurons respond to activated Hoxb8 microglia?
  • How do the two types of microglia interact to modulate behavior?
  • Can similar mechanisms induce anxiety in humans?

Answering these questions will require further research using techniques like optogenetics along with detailed analysis of the molecular interactions between microglia and neurons. This promises to provide an even deeper understanding of how the brain regulates complex behaviors like anxiety.

Conclusions

  • Activating a specific type of brain immune cell called Hoxb8 microglia can rapidly trigger anxiety and grooming behaviors in mice
  • The effects depend on which brain region is stimulated, with some areas inducing anxiety, others grooming, and some both
  • Hoxb8 microglia appear to modulate the activity of nearby neurons when activated
  • Different types of microglia may play opposing roles in regulating these behaviors
  • Understanding these mechanisms could lead to new approaches for treating anxiety disorders and related conditions
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