Hippocampal astrocytic GAT-3 blockade impairs aversive memory dynamics

Astrocyte–neuron communication is essential for synaptic function and behavior. Astrocytes express neurotransmitter transporters that regulate extracellular neurotransmitter levels. GAT-3 mediates GABA uptake and contributes to inhibitory tone, thereby regulating hippocampal neuronal excitability. Here, we investigated the role of hippocampal GAT-3 in aversive inhibitory avoidance (IA) memory. To assess its role in memory consolidation, SNAP-5114, a GAT-3 inhibitor, was administered into the rat hippocampus at different time points around training. SNAP administered 15 min before or 30 min after training impaired long-term memory (LTM) in female rats, whereas more distant administration times had no effect. Administration 15 min before training in males confirmed the findings observed in females. We next examined whether GAT-3 activity was required for LTM expression. SNAP administered 15 min before the IA test, 24 h after training, impaired LTM expression in both sexes. Finally, SNAP administered 15 min before the short-term memory (STM) test, 2 h after training, impaired STM expression in males but, as expected, did not affect subsequent LTM. Together, these findings indicate that astrocytic GAT-3 contributes to the consolidation and expression of aversive memory in both sexes, supporting a role for astrocytic neurotransmitter transporters in memory dynamics and motivating further investigation of their contribution to memory persistence and modification.