Differential Effects of Hippocampal Astrocytic Glutamate Uptake Modulation on Aversive Memory Formation and Expression

Abstract

The control of glutamate concentration in the synaptic gap is crucial for neuronal communication, preventing excitotoxicity from excessive receptor activation. There are specific transporters in the brain that are responsible for maintaining glutamate homeostasis. The glutamate transporter GLT-1 is mainly localized in astrocytes, and its expression is particularly abundant in the hippocampus. This study explored the role of GLT-1 in memory phases using contextual fear conditioning (CFC) and inhibitory avoidance (IA) tasks. Dihydrokainic acid (DHK), a selective GLT-1 inhibitor, was injected into the dorsal hippocampus of female rats at different times around aversive learning. DHK administration 2 h after weak CFC or IA training sessions improved long-term memory (LTM) formation. However, DHK administration around strong training sessions did not affect consolidation in either task. Moreover, the DHK application 15 min before test sessions impaired short-term memory (STM) and LTM expression in both tasks. In contrast, the antibiotic ceftriaxone (CFT), which increases GLT-1 expression, did not affect the expression of aversive memories. This study highlights the critical role of hippocampal astrocytic glutamate uptake in the formation and expression of aversive memories.