Mouse Prefontal Cortex Astrocyte Proteome

Anxiety disorders are among the most common and disabling mental health disorders worldwide with inadequate therapeutic options. Numerous clinical and research studies indicate essential neuronal contribution to anxiety, yet the mechanisms of non-neuronal cells governing this emotional state remain poorly understood. Here, we show that non-neuronal astrocytes in the medial prefrontal cortex (mPFC) encode anxiogenic environmental cues. Silencing mPFC astrocyte Ca2+ signaling heightens anxiety-like behavior and disrupts the balance between excitatory and inhibitory neuronal population activity. Moreover, this effect is differentially pronounced across behaviorally tuned neuronal subpopulations on single cell and network levels. Using cell type-specific proximity-dependent biotinylation approaches, we further identified significant protein expression changes in astrocytes and at the astrocyte-neuron interface within the mPFC.