Formation, expression and reconsolidation of aversive memory: the role of astrocytic glutamate uptake in the contextual fear conditioning task

RENFIJES M; RIBOLDI, J; CORREA, J; VIOLA, H

Congreso; Sociedad Argentina de Neurociencias; 2023

According to the tripartite synapse concept, astrocytes are integral elements involved in synaptic function and this makes them important players in brain function and animal behavior. One of the most importantfunctions of astrocytes in the brain is their control in the permanence of glutamate in the synaptic gap that requires strict control to avoid excitotoxicity, being this control exerted by the action of specific transportersexpressed throughout the brain. The objective of this work was to study the role of Glutamate transporter GLT–1, specifically located in astrocytes, using contextual fear conditioning (CFC) and Inhibitory avoidance (IA)tasks. We infused dihydrokainic acid (DHK), a selective GLT-1 inhibitor, into the rat hippocampus to affect different stages of memory. A strong CFC training session induced long-term memory (LTM) formation, and it wasobserved that hippocampal GLT-1 inhibition around training did not affect consolidation. However, the expression of either short-term memory (STM) or LTM was impaired, when DHK was applied 15 minutes before thesetest sessions. Also, if applied 15 minutes after a reactivation session, DHK impairs CFC reconsolidation. In contrast, after a weak CFC training session, which only induced STM, hippocampal inhibition of GLT-1 showed promotion of LTM formation. The effects of DHK on memory processes cannot be attributed to changes in rat locomotor activity or anxiety-like states, since DHK administration in the hippocampus 15 min prior to an open field followed by an elevated plus-maze session yielded similar results to those registered in control rats. In conclusion, we found that GLT-1 blockage close to training time helps to consolidate CFC memory induced by weak training but does not alter the consolidation mechanisms induced by strong training. However, the blockage of this transporter interferes with the expression of memory and with its reconsolidation. Our findings describe the full dynamics of an aversive memory under the hippocampal effects of astroglial glutamate uptake blockage, which could represent a possible site of action for the development of new treatments for the post-traumatic stress and cognitive impairment.