Prefrontal cortex astrocytes modulate distinct neuronal populations to control anxiety-like behavior

Area of Science:

• Neuroscience
• Cell Biology
• Behavioral Science

Background:

• Astrocytes regulate neural circuits and complex behaviors.
• Limited understanding of astrocyte regulation of specific neuronal subpopulations within a single brain region.

Purpose of the Study:

• Investigate how medial prefrontal cortex (mPFC) astrocytes encode anxiogenic cues.
• Elucidate astrocyte-neuron interactions in anxiety-like behavior.

Main Methods:

• In vivo calcium imaging in freely behaving mice.
• Genetic silencing of astrocyte Ca2+ signaling.
• Cell type-specific proximity biotinylation.
• Proteomic analysis of astrocytes and astrocyte-neuron interfaces.

Main Results:

• mPFC astrocytes encode anxiogenic environmental cues.
• Silencing mPFC astrocyte Ca2+ signaling exacerbates anxiety-like behavior.
• Opposing functional shifts in excitatory and inhibitory neurons observed.
• Differential modulation of anxiety-tuned neuronal subpopulations by astrocytes.
• Identified proteomic changes in astrocytes and at the astrocyte-neuron interface.

Conclusions:

• mPFC astrocytes play a critical role in encoding anxiety.
• Heterogeneous astrocyte-neuron interactions are behaviorally relevant.
• Findings offer insights into the pathophysiology of emotional disorders.