CENTRAL AMYGDALA ASTROCYTES ARE REQUIRED FOR REMOTE FEAR MEMORY

A fearful experience can leave an indelible scar, and we pay for its survival with a lifelong memory. Fear memories undergo systems-level reorganization, shifting from fragile recent memories into stable remote ones. While the central amygdala (CeA) is well known for its role in recent fear memory, accumulating evidence suggests it also contributes to remote fear memory expression. Astrocytes, integral components of the tripartite synapse, are increasingly recognized for their roles in modulating synaptic functions and memory formation. Despite well-characterized neuronal circuitry in the CeA, how astrocytes contribute to fear memory stabilization and expression — particularly at remote time points — remains poorly understood.
Here, we investigated the contribution of CeA astrocytes and their underlying mechanisms to modulating fear memory retrieval using multidisciplinary approaches, including in vivo Ca²⁺ fiber photometry, ex vivo electrophysiology, and viral-assisted astrocyte manipulation. During memory retrieval tests following auditory fear conditioning, elevated CeA astrocytic calcium responses to the conditioned stimulus (tone) were observed exclusively during remote fear memory retrieval (28 days post-conditioning), but not during recent fear memory retrieval (1 day post-conditioning). Furthermore, inhibition of CeA astrocytes not only diminished the enhanced inhibitory transmission within the CeA microcircuit following remote fear memory retrieval, but also impaired the remote fear memory expression. Together, our findings demonstrate that CeA astrocytes are required for remote fear expression and suggest that astrocyte-mediated modulation of local inhibitory circuitry supports the long-term expression of learned fear.