Anxiety is Induced by Activating Microglia, the Immune Cells of the Brain
Post by Rebecca Hill
The takeaway
Hoxb8 microglia, the support cells of the brain created by the Hoxb8 gene, play a role in regulating anxiety. When these microglia are activated with light using optogenetics in certain areas of the brain, mice display anxious grooming and freezing behaviors.
What's the science?
Hoxb8 is a gene involved in creating certain microglia, the immune support cells of the brain, but the function of both have yet to be fully elucidated. When the Hoxb8 gene is mutated, or these microglia are removed in mice, they show chronic anxious behaviors and excessive grooming. Recently, in Molecular Psychiatry, Nagarajan and colleagues investigated whether activating these microglia in certain areas of the brain using light has an effect on anxious behaviors in mice.
How did they do it?
To activate the Hoxb8 microglia, the authors used optogenetic stimulation — using light to control the activity of certain cells in the brain. They activated Hoxb8 microglia in specific areas of the brain such as the dorsomedial striatum, the medial prefrontal cortex, the amygdala, and the hippocampus, which have previously been shown to control anxiety in mice. While stimulating these areas of the brain, they measured the behavioral effects; changes in grooming and other anxiety behaviors in different situations. They ran mice through several behavioral tests, measuring the anxiety-behaviors 2 minutes before stimulation, during the 2 minutes of stimulation, then the 2 minutes after stimulation. To measure anxiety levels, they used both a maze and an open field area to test how much time mice would spend in the fear-inducing open areas of the chambers as opposed to comfortable enclosed areas.
What did they find?
Mice groomed themselves when the dorsomedial striatum and the medial prefrontal cortex were stimulated and demonstrated higher levels of anxiety when areas in the amygdala were stimulated. This suggests that grooming is controlled by the former two areas, while anxiety is controlled by the latter area. When the microglia in the hippocampus were stimulated, mice showed both grooming and anxiety behaviors, in addition to increased freezing, which suggests the hippocampus is involved in controlling all three behaviors related to anxiety. Interestingly, when both Hoxb8 microglia and microglia not created by Hoxb8 (non-Hoxb8 microglia) were stimulated at the same time, mice did not display any anxiety behaviors at all. This suggests that Hoxb8 and non-Hoxb8 microglia work together with opposing effects, to control anxiety. Hoxb8 microglia turn off anxiety behaviors (like brakes on a car), and non-Hoxb8 microglia turn these behaviors on (like the accelerator).
In order to reconcile previous findings of anxiety increasing when Hoxb8 microglia are removed, with the current finding that activating Hoxb8 microglia also causes anxiety increase, the authors suggest that optogenetic activation of these Hoxb8 microglia might somehow cancel out their inhibitory effects on anxiety behaviors. While these mechanisms are still not fully understood, they likely involve the neighboring neurons that were activated when the Hoxb8 microglia were stimulated. Either way, these microglia are key in regulating anxiety, potentially in both directions.
What's the impact?
This study is the first to show that Hoxb8 microglia can be used to control anxiety behaviors using optogenetic techniques. It also suggests the reason for having both Hoxb8 and non-Hoxb8 microglia is to finely control anxiety behavior. Anxiety and related mental disorders are widespread both among adolescents and adults, so understanding the way it works within the brain is crucial so that we can better treat chronic anxiety. Studies like these could play a huge part in creating treatments that target these specific microglia and areas of the brain for chronic anxiety disorders.
