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Astrocyte molecular changes during basolateral amygdala-related emotional behaviors [set7]

ABSTRACT: Astrocytes tile the central nervous system (CNS) and have fundamental roles in physiology and disease, yet there remain open questions about their contributions to physiological and pathological processes in the CNS. The basolateral amygdala (BLA) integrates rewarding and aversive stimuli and is integral to mood regulation and emotional behaviors. As many past studies have focused on neurons in the BLA, the contribution of BLA astrocytes to emotional behaviors is largely unknown. A major bottleneck has been the paucity of reliable tools to explore astrocyte functions and molecular mechanisms in vivo. This shortfall has been addressed by recent developments in the field reporting approaches to systematically explore the role of astrocytes with improved tools. Here, we used several such tools to elucidate BLA astrocytic changes during emotional behavioral responses. Applying several mouse models of stress (negative emotional triggers) and astrocyte-specific adenoassociated viruses (AAVs), [Ca2+] imaging, RNA sequencing, and proteomics, we explored the role of astrocytes at the molecular and cellular level in the BLA. We analyzed the data to evaluate how astrocytes might be exploited in vivo to improve behavioral outcomes in emotion-related disorders such as anxiety and depression.

ORGANISM(S): Mus musculus

PROVIDER: GSE326603 | GEO | 2026/06/18

REPOSITORIES: GEO

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Astrocyte molecular changes during basolateral amygdala-related emotional behaviors [set6]

Project description:Astrocytes tile the central nervous system (CNS) and have fundamental roles in physiology and disease, yet there remain open questions about their contributions to physiological and pathological processes in the CNS. The basolateral amygdala (BLA) integrates rewarding and aversive stimuli and is integral to mood regulation and emotional behaviors. As many past studies have focused on neurons in the BLA, the contribution of BLA astrocytes to emotional behaviors is largely unknown. A major bottleneck has been the paucity of reliable tools to explore astrocyte functions and molecular mechanisms in vivo. This shortfall has been addressed by recent developments in the field reporting approaches to systematically explore the role of astrocytes with improved tools. Here, we used several such tools to elucidate BLA astrocytic changes during emotional behavioral responses. Applying several mouse models of stress (negative emotional triggers) and astrocyte-specific adenoassociated viruses (AAVs), [Ca2+] imaging, RNA sequencing, and proteomics, we explored the role of astrocytes at the molecular and cellular level in the BLA. We analyzed the data to evaluate how astrocytes might be exploited in vivo to improve behavioral outcomes in emotion-related disorders such as anxiety and depression.

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Project description:Astrocytes and neurons coexist and interact in the CNS1,2. Given that many signaling and pathological events are protein-driven, identifying astrocyte and neuron proteomes is essential for elucidating the complex protein networks that dictate their respective contributions to physiology and disease. Here, we used cell- and subcompartment-specific proximity-dependent biotinylation3 to study the proteomes of striatal astrocytes and medium spiny neurons (MSNs) in vivo. We evaluated cytosolic and plasma membrane compartments for astrocytes and MSNs, revealing how these cells differ at the protein level and in their core signaling machinery. We assessed subcellular compartments of astrocytes including end feet and processes to reveal the molecular basis of essential astrocyte signaling and homeostatic functions. Unexpectedly, SAPAP3 proteins (gene; Dlgap3) associated with obsessive compulsive disorder (OCD) and repetitive behaviors4-11 were detected at equivalent levels in striatal astrocyte and MSN plasma membrane and cytosolic compartments. Astrocytic expression was confirmed by RNA-seq, fluorescence in situ hybridization and immunohistochemistry. Furthermore, genetic rescue experiments combined with behavioral analyses and proteomics in a mouse model4 of OCD lacking SAPAP3 revealed contributions of SAPAP3 in astrocytes and MSNs to repetitive and anxiety-related OCD behaviors. Our data define how astrocytes and neurons differ at the protein level and in their major signaling pathways, how astrocyte proteomes vary between physiological subcompartments, and how specific astrocyte and neuronal molecular mechanisms contribute to a psychiatric disease. Targeting both astrocytes and neurons together is likely to be therapeutically effective in complex CNS disorders.

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