Astrocytes enable amygdala neural representations supporting memory
Publication date: 11/02/2026
Authors: Olena Bukalo, Ruairi O’Sullivan, Yuta Tanisumi, Adriana Mendez, Chase Weinholtz, Sydney Zimmerman, Victoria Offenberg, Olivia Carpenter, Hrishikesh Bhagwat, Sophie Mosley, John J. O’Malley, Kerri Lyon
Journal: Nature Neuroscience
Commentary: Fear-memory retrieval and extinction depend on neuronal representations within the basolateral amygdala (BLA), but the contribution of non-neuronal cells remains poorly understood. Bukalo and colleagues demonstrate that BLA astrocytes regulate the neural representations underlying fear-memory expression and extinction. A major strength of the study is its multilevel design, integrating population and single-cell Ca²⁺ imaging, chemogenetics, viral approaches, electrophysiology, behavioural testing, and circuit-specific analyses. The conclusions are therefore supported by the convergence of observational and causal evidence. Using cued fear conditioning and in vivo fibre photometry, the authors showed that astrocytic Ca²⁺ activity dynamically tracked fear. Conditioned stimulus-evoked responses emerged during memory retrieval, diminished as extinction progressed, paralleled reductions in freezing, and reappeared during fear renewal. Two-photon imaging revealed heterogeneous astrocytic events with distinct extinction-related trajectories. Moreover, astrocytic activity permitted decoding of conditioned stimulus presentation, indicating that memory-related information is represented within astrocytic populations. The causal relevance of these signals was established through complementary manipulations. Chronic suppression of astrocytic Ca²⁺ signalling using the calcium extruder CalEx reduced fear-memory retrieval. Temporally restricted disruption of astrocytic Ca²⁺ dynamics through hM3Dq similarly attenuated conditioned freezing, whereas hM4Di-mediated increases in astrocytic activity enhanced fear expression. Notably, both upward and downward perturbations impaired extinction-memory formation, suggesting that extinction requires precisely regulated astrocytic Ca²⁺ dynamics rather than simply high or low activity. By combining astrocyte manipulation with neuronal imaging, the authors showed that astrocytes maintain BLA neuronal ensembles encoding the conditioned stimulus and enable memory readout through BLA projections to the prefrontal cortex. Overall, this work moves beyond neuron-centered models of aversive memory by identifying astrocytes as integral components of amygdala circuitry governing fear retrieval and extinction. The findings provide a new framework for understanding persistent fear and highlight overlooked cellular mechanisms potentially relevant to anxiety and trauma-related disorders.
Commented by: Giulia Chiacchierini
DOI: https://doi.org/10.1038/s41586-025-10068-0
