Fear memory expression and reconsolidation depend on hippocampal astrocytic glutamate uptake in male rats

The control of glutamate levels in the synaptic gap is crucial for neuronal communication, as it prevents excitotoxicity from excessive receptor activation. Glutamate transporters GLT-1 are mainly localized in astrocytes and its expression is particularly abundant in the hippocampus (Hp). In this study, we explored the role of GLT-1 in consolidation, expression and reconsolidation of memory, using contextual fear conditioning (CFC) task. Dihydrokainic acid (DHK), a selective GLT-1 inhibitor, was injected into the dorsal Hp of male rats at different times around aversive learning. DHK administration 15 min after a weak CFC training session promoted long-term memory (LTM) formation. However, DHK administration around strong CFC training sessions did not affect memory consolidation. Moreover, DHK infusion 15 min before the LTM test session impaired CFC memory expression. Importantly, if applied 15 min after a reactivation session, DHK impairs CFC reconsolidation. In contrast, the antibiotic ceftriaxone (CFT), which increases GLT-1 expression, did not affect the consolidation or the expression of fear memory. The effects of DHK and CFT on memory were not due to changes in locomotor activity or anxiety-like state of rats. In conclusion, our findings indicate that inhibition of hippocampal astroglial glutamate uptake impairs the expression and reconsolidation of aversive memory without impairing its consolidation, and highlight potential therapeutic avenues for neuropsychiatric conditions, including phobias, post-traumatic stress disorder, and cognitive deficits.