D-059 | Astrocitic GLT-1 in Aversive Memories: Differential Effects of its Blockage or Upregulation

Cognition, Behavior, and Memory
Author: Matías Martín Renfijes | Email: matias.mrenfijes5@gmail.com

Matías Martín Renfijes^1°2°, Juan Gabriel Riboldi^1°2°3°, Josefina Iribarne^1°,  Haydee Ana María Viola^1°2°3°

^1° Facultad de Medicina, Instituto de Biología Celular y Neurociencia “Prof. E. De Robertis” (IBCN), UBA-CONICET, Buenos Aires, Argentina,
^2° Instituto Tecnológico de Buenos Aires, Buenos Aires, Argentina.
^3° Departamento de Fisiología, Facultad de Ciencias Exactas y Naturales, Biología Molecular y Celular “Dr. Héctor Maldonado” (FBMC), University of Buenos Aires (UBA), Buenos Aires, Argentina

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. GLT-1 transporters are mainly localized in astrocytes and its expression is particularly abundant in the hippocampus. This study explored the role of GLT-1 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 rats at different time around aversive learning. DHK administration around a weak CFC or IA training sessions promoted long-term memory (LTM) formation. However, DHK administration around strong trainings that induced LTM, did not affect consolidation in either task. Moreover, the application of DHK 15 minutes before test sessions impaired the expression of short-term memory and LTM in both tasks. DHK administered 15 minutes after a reactivation session impaired CFC reconsolidation. In contrast, the antibiotic ceftriaxone (CFT), which increases GLT-1 expression, did not affect the expression of aversive memory. The effects of DHK and CFT on memory were not due to changes in locomotor activity or anxiety-like state of rats. This study highlights the critical role of hippocampal astrocytic glutamate uptake in the formation and persistence of aversive memories.