Astrocytic determinant of the fate of long-term memory.

Abstract

While some vivid memories are unyielding and unforgettable, others fade with time. Astrocytes are recognized for their role in modulating the brain's environment and have recently been considered integral to the brain's information processing and memory formation. This suggests their potential roles in emotional perception and memory formation. In this study, we delve into the impact of amygdala astrocytes on fear behaviors and memory, employing astrocyte-specific optogenetic manipulations in mice. Our findings reveal that astrocytic photoactivation with channelrhodopsin-2 (ChR2) provokes aversive behavioral responses, while archaerhodopsin-T (ArchT) photoactivation diminishes fear perception. ChR2 photoactivation amplifies fear perception and fear memory encoding but obstructs its consolidation. On the other hand, ArchT photoactivation inhibits memory formation during intense aversive stimuli, possibly due to weakened fear perception. However, it prevents the decay of remote fear memory over three weeks. Crucially, these memory effects were observed when optogenetic manipulations coincided with the aversive experience, indicating a deterministic role of astrocytic states at the exact moment of fear experiences in shaping long-term memory. This research underscores the significant and multifaceted role of astrocytes in emotional perception, fear memory formation, and modulation, suggesting a sophisticated astrocyte-neuron communication mechanism underlying basic emotional state transitions of information processing in the brain.