Astrocytes in Fear Memory Processing: Molecular Mechanisms Across the Amygdala-Hippocampus-Prefrontal Cortex Network

Fear memory is a critical adaptive process that enables organisms to avoid potential threats and survive in complex environments. Traditionally viewed as a neuronal phenomenon, emerging evidence has demonstrated that astrocytes play a fundamental role in fear memory acquisition, consolidation, extinction, and retrieval across the distributed neural network encompassing the amygdala, hippocampus, and prefrontal cortex. This review presents recent advances in our understanding of the molecular mechanisms by which astrocytes modulate fear memory processing within the tripartite circuit. We examine how astrocytes contribute to synaptic plasticity, neurotransmitter regulation, metabolic support, and intercellular communication during the different phases of fear memory processing. Particular emphasis is placed on the region-specific functions of astrocytes, their dynamic interactions with neurons, and their therapeutic implications for treating fear-related disorders such as post-traumatic stress disorder (PTSD) and anxiety disorders. The integration of cutting-edge technologies, including spatial transcriptomics, optogenetics, and chemogenetics, has revealed sophisticated astrocyte-neuron communication mechanisms that challenge the traditional neuron-centric view of memory processing.