ASTROCYTE-MEDIATED CONTROL OF FEAR MEMORY FATE DETERMINATION

Animals exploit regularities in the environment by storing memories and later using them to guide behavior. Astrocytes may modulate neuronal metaplastic states, thereby influencing memory formation during highly salient experiences, such as intense fear. Here, we combined a classical fear-conditioning paradigm with in vivo astrocyte optogenetic manipulations and fiber photometry recordings, and ex vivo measurements, to investigate the role of amygdala astrocytes in fear memory. First, astrocyte activity was perturbed with channelrhodopsin-2 (ChR2) during foot-shock conditioning. Memory tests revealed that memory was normally formed 6 minutes after conditioning but abolished after 24 hours, indicating intact short-term memory but impaired consolidation into long-term memory. Next, astrocytes were perturbed using Archaerhodopsin-T (ArchT). Under weak shock conditions, ArchT had no effect on 24-hour memory. Increasing the shock intensity produced stronger memory, reflecting graded encoding of stimulus strength. This intensity discrimination was lost when ArchT was activated during the shocks. Forgetting over time is adaptive, preventing the waste of memory capacity on events unlikely to recur. Three weeks after conditioning, memory was reduced, indicating forgetting. However, ArchT activation during conditioning enhanced 3-week retention of memories. Because both optogenetic manipulations were applied only during the conditioning period, the long-term fate of days-to-weeks memory appears to be determined within a short time window following the high-valence event. These perturbation experiments demonstrate that astrocytes can modulate memory formation. To assess whether astrocytes show physiologically relevant activity, astrocyte activity patterns were assessed in vivo and ex vivo to identify dynamics that underlie their possible roles in memory modulation.