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Updated: Apr 15, 2026
Optogenetic Manipulation of Neuronal Activity to Modulate Behavior in Freely Moving Mice
Published on: October 27, 2020
Microglia respond to and induce anxiety and grooming in mice using calcium signaling
Naveen Nagarajan1,2, Mario R Capecchi3
1Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA. naveen.nagarajan@louisville.edu.
Abstract:
Disruption of the mouse Hoxb8 gene causes chronic anxiety and pathological over-grooming resulting from defective Hoxb8 microglia. Furthermore, optogenetic stimulation of Hoxb8 microglia in specific regions of the brain induces elevated anxiety and/or grooming. Herein we show that the molecular signals for inducing anxiety and/or grooming in response to optogenetic activation are calcium ions. Conversely, induction of grooming and anxiety in mice produces calcium transients within microglia. Unexpectedly, calcium transients are not produced in Hoxb8 mutant mice in response to the induction of these behaviors. The likely cause for this lack of response by Hoxb8 mutant mice to induced grooming is the presence of high constitutive levels of free calcium within Hoxb8 mutant microglia resulting from the gene disruption. These calcium ions, in turn, serve as relentless signals to increase anxiety and grooming leading to chronic anxiety and pathological overgrooming in Hoxb8 mutant mice. Thus, we have shown that calcium signaling is used by microglia: 1) to induce anxiety and/or grooming by optogenetic stimulation of Hoxb8 microglia in WT mice, 2) to respond by microglia to the induction of both behaviors in WT mice and 3) as the causative agent for producing chronic anxiety and pathological overgrooming in Hoxb8 mutant mice.
Insights
Disruption of the Hoxb8 gene in mice leads to chronic anxiety and over-grooming due to defective microglia. Calcium signaling within these microglia is identified as the key molecular mechanism driving these behaviors.
Area of Science:
- Neuroscience
- Cell Biology
- Genetics
Background:
- Disruption of the mouse Hoxb8 gene is linked to chronic anxiety and pathological over-grooming.
- These behavioral changes are associated with defective Hoxb8 microglia.
- Optogenetic stimulation of Hoxb8 microglia can induce anxiety and grooming behaviors.
Purpose of the Study:
- To investigate the molecular signals mediating anxiety and grooming induced by Hoxb8 microglia.
- To understand the role of calcium ions in microglial function related to anxiety and grooming.
- To elucidate the mechanism by which Hoxb8 gene disruption leads to chronic behavioral deficits.
Main Methods:
- Optogenetic stimulation of Hoxb8 microglia in wild-type (WT) and Hoxb8 mutant mice.
- Monitoring calcium ion transients within microglia in response to stimulation and behavioral induction.
- Analyzing the effects of gene disruption on microglial calcium signaling.
Main Results:
- Calcium ions were identified as the molecular signals inducing anxiety and grooming via optogenetic activation of Hoxb8 microglia in WT mice.
- Induction of grooming and anxiety in WT mice resulted in microglial calcium transients.
- Hoxb8 mutant mice showed a lack of calcium transients in response to induced behaviors, likely due to high constitutive calcium levels.
Conclusions:
- Calcium signaling is crucial for microglia to induce and respond to anxiety and grooming behaviors.
- Elevated constitutive calcium levels in Hoxb8 mutant microglia cause chronic anxiety and pathological over-grooming.
- The Hoxb8 gene plays a critical role in regulating microglial calcium homeostasis and associated behaviors.
